GliomaPhase 2VEG102857NCT00350727

Pazopanib In Combination With Lapatinib In Adult Patients With Relapsed Malignant Glioma

A Phase 2 study testing pazopanib and lapatinib in people with Glioma, run by GlaxoSmithKline.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study is being conducted to characterize the safety/tolerability of pazopanib and lapatinib when administered in combination with enzyme-inducing anticonvulsants in patients with recurrent Grade III or IV malignant gliomas. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioma
What is being tested?: pazopanib and lapatinib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 75 participants
Where: No sites listed yet
Study dates: Dec 2006to Dec 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Phase I
Patients are on EIAC for a minimum of 15 days. Patients may be on more than one anti-convulsant (AC). At least one of the ACs must be an EIAC.
Patients with anaplastic astrocytoma, anaplastic oligodendroglioma, mixed anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma at recurrence
Patients whose diagnostic pathology confirmed these pathologies will not need re-biopsy
Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to Grade III or IV malignant glioma Phase II
Patients must have histologically confirmed glioblastoma multiforme or gliosarcoma in first or second recurrence.

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Patients may not have received more than two prior cytotoxic chemotherapy containing regimen.
Patients must not have received prior treatment with VEGFR, ErbB1, ErbB2 inhibitors including but not limited to PTK-787, Sorafenib, Sutent, Tarceva, Iressa, Erbitux, and Herceptin. Prior Avastin therapy is permitted provided three months has elapsed before Day 1, Treatment Period 1.
Tumor tissue must be analyzed for PTEN and epidermal growth factor receptor (EGFR) vIII prior to dosing.
Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to Grade IV malignant glioma.
Patients must not be on an EIAC. NOTE: Once the (optimally tolerated regimen) OTR in Phase I is determined and all patients in the expanded cohort have completed 1 treatment period then patients on EIAC may be enrolled in the Phase II component of the study.
Phase I and II
Male or female, age at least 18 years of age.
Eastern Cooperative Oncology Group (ECOG) status 0 to 1 as per protocol.
Clinical lab results as per protocol
Has a left ventricular ejection fraction (LVEF) at least 50% based on echocardiogram (ECHO) or Multi Gated Aquisition (MUGA) or within the institutional normal range.
Adequate renal function
Creatinine clearance more than 50 mL/min as calculated by the Cockcroft-Gault formula as per protocol.
Urine Protein Creatinine (UPC) ratio of less than or equal to 1 as per protocol.
Able to swallow and retain oral medications.
A woman is eligible to enter and participate in the study if she is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:
Has had a hysterectomy,
Has had a bilateral oophorectomy (ovariectomy),
Has had a bilateral tubal ligation,
Is post-menopausal (total cessation of menses for at least 1 year)
Childbearing potential, has a negative serum pregnancy test at screening, and agrees to use adequate contraception. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:
An intrauterine device (IUD) with a documented failure rate of less than 1% per year.
Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female.
Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
A man with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study.
If sexually active, patients will continue the recommended contraceptive measures for the duration of the treatments and for 28 days following discontinuation of therapy.
Signed informed consent approved by the Institutional Review Board prior to patient entry.

Who cannot join

Poorly controlled hypertension as per protocol. NOTE: Initiation or adjustment of BP medication is permitted prior to study entry provided that patient has two consecutive BP readings less than 140/90 mmHg each separated by a minimum of 24 hrs. These readings need to be collected prior to enrolment.
Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive cardiac failure, poorly controlled hypertension, history of labile hypertension, history of poor compliance with antihypertensive regimen, chronic renal disease, or active uncontrolled infection) that could compromise participation in the study.
History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within three months of Day 1, Treatment Period 1.
Has Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system as per protocol.
QTc prolongation defined as a corrected QT (QTc) interval greater than or equal to 470 milliseconds.
History of venous or arterial thrombosis within 3 months of Day 1, Treatment Period 1.

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Current use of therapeutic warfarin. NOTE: both low molecular weight heparin and prophylactic low-dose warfarin are permitted; however, prothrombin time/partial thromboplastin time (PT/PTT) must meet above inclusion criteria.
Excessive risk of bleeding as defined by stroke within the prior 6 months, history of central nervous system (CNS) or intraocular bleed, or septic endocarditis.
Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative Grade 1 hemorrhage.
Active systemic bleeding, such as gastrointestinal bleeding or gross hematuria.
Female patients who are pregnant or breast feeding.
Acute or chronic liver disease (i.e., hepatitis, cirrhosis).
Patients who received investigational drugs less than 21days prior to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy.
Patients who received chemotherapy less than or equal to 21days prior (6 weeks for prior nitrosourea or mitomycin C) to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy.
Patients who received radiation therapy less than or equal to 12 weeks prior to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy as per protocol.
Patients who received biologic, immunotherapeutic or cytostatic agents less than or equal to 14 days prior to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy.
Patient is less than 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant or requiring active intervention. Patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Surgical resection of brain tumor or any other surgery less than or equal to 21 days prior to Day 1, Treatment Period 1, or who have not recovered from side effects of such a procedure. Patients who undergo stereotactic biopsy less than or equal to 14 days prior to Day 1 of Treatment Period 1, or who have not recovered from side effects of such a procedure.
Patients with any Grade of intraparenchymal CNS hemorrhage. Exceptions include Grade 1 intraparenchymal hemorrhage in the immediate post-operative period, or Grade 1 intraparenchymal hemorrhage that has been stable for at least 3 months.
Patients unwilling to or unable to comply with the protocol.
Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with patient safety or obtaining informed consent.
History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. Has any unresolved bowel obstruction or diarrhea.
Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
Is on any specifically prohibited medication or requires any of these medications during treatment.

About this study

Official title: Phase I and II, Open-Label, Multi-Center Trials of Pazopanib in Combination With Lapatinib in Adult Patients With Relapsed Malignant Glioma

Read the detailed description

Conditions: Glioma
Being tested: pazopanib, lapatinib
Keywords: relapsed, lapatinib, Pazopanib, glioblastoma
Medical subject headings: Glioma, Recurrence, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pazopanibDrug
Pazopanib is a novel compound being developed for the treatment of various cancers.
lapatinibDrug
Also called pazopanib
Lapatinib is a novel compound being developed for the treatment of various cancers.

Study groups in NCT00350727
Study group	Role	What they receive
Combination	Experimental	Pazopanib and Lapatinib in combination. Subjects remain on treatment until disease progression or withdrawal from study. Receives: Drug: pazopanib; Drug: lapatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Measured: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Measured: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. bpm, beats per minute.
Measured: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Measured: Baseline to study completion (up to 878 days for Phase II)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Measured: Baseline to study completion (up to 844 days for Phase I)
Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Measured: Baseline to study completion (up to 844 days for Phase I)
Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose
A dose-limiting toxicity (DLT) is defined as predefined adverse events or events that prevented participants from receiving 75% of their scheduled doses or from starting their next treatment period. The dose at which no more than 1 out of 6 participants experiences a DLT is defined as the optimally tolerated regimen. The OTR is important because it determines the highest dose combination that can be given without significant toxicity.
Measured: Cycle 1 in Phase I (up to Day 28)
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Measured: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Measured: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Measured: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Progression-free Survival at 6 Months
Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used. The participants who are still alive and whose follow-up extends to at least 6 months are considered At Risk.
Measured: Date of the first dose of study drug to 6 months

Secondary outcomes (5)

Phase I: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, the Time to Maximum Observed Concentration (Tmax) and C24 of Pazopanib and Lapatinib When Administered in Combination With EIAC.
Measured: Completed during first cycle of treatment.
Phase II: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, Tmax, and C24 of Pazopanib and Lapatinib, as Appropriate, When Administered Together in Combination With Non-EIAC.
Measured: Completed during first cycle of treatment.
Phase II: Plasma Concentrations of the Circulating Biomarkers VEGF, sVEGFR-1, and sVEGFR-2.
Measured: Completed during first cycle of treatment.
Progression-free Survival
Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used.
Measured: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)
Time to Disease Progression or Death Due to Any Cause
Measured: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2006Dec 2009

First posted11 Jul 2006 (estimated)
Study startDec 2006
Primary completionDec 2009
Study completionDec 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for GliomaStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 75 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00350727
Sponsor's protocol ID: VEG102857
Acronym: VEG102857
Status last verified: May 2012
First submitted: 10 Jul 2006
Last updated: 19 Apr 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

de Jonge MJ, Hamberg P, Verweij J, Savage S, Suttle AB, Hodge J, Arumugham T, Pandite LN, Hurwitz HI. Phase I and pharmacokinetic study of pazopanib and lapatinib combination therapy in patients with advanced solid tumors. Invest New Drugs. 2013 Jun;31(3):751-9. doi: 10.1007/s10637-012-9885-8. Epub 2012 Oct 6.
PubMed 23054212

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma

All Glioma trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I and II, Open-Label, Multi-Center Trials of Pazopanib in Combination With Lapatinib in Adult Patients With Relapsed Malignant Glioma
ClinicalTrials.gov ID: NCT00350727
Acronym / sponsor ID: VEG102857 / VEG102857
Conditions: Glioma
Keywords: relapsed, lapatinib, Pazopanib, glioblastoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 75 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: Dec 2006
Primary completion: Dec 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 11 Jul 2006 (estimated)
Results: Posted 20 Jun 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Combination	Experimental	Drug: pazopanib, Drug: lapatinibPazopanib and Lapatinib in combination. Subjects remain on treatment until disease progression or withdrawal from study.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (33 listed)

Phase I
Patients are on EIAC for a minimum of 15 days. Patients may be on more than one anti-convulsant (AC). At least one of the ACs must be an EIAC.
Patients with anaplastic astrocytoma, anaplastic oligodendroglioma, mixed anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma at recurrence
Patients whose diagnostic pathology confirmed these pathologies will not need re-biopsy
Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to Grade III or IV malignant glioma Phase II

Key exclusion criteria (24 listed)

Poorly controlled hypertension as per protocol. NOTE: Initiation or adjustment of BP medication is permitted prior to study entry provided that patient has two consecutive BP readings less than 140/90 mmHg each separated by a minimum of 24 hrs. These readings need to be collected prior to enrolment.
Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive cardiac failure, poorly controlled hypertension, history of labile hypertension, history of poor compliance with antihypertensive regimen, chronic renal disease, or active uncontrolled infection) that could compromise participation in the study.
History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within three months of Day 1, Treatment Period 1.
Has Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system as per protocol.
QTc prolongation defined as a corrected QT (QTc) interval greater than or equal to 470 milliseconds.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pazopanibPazopanib is a novel compound being developed for the treatment of various cancers.	Drug	Combination
lapatinibAlso: pazopanibLapatinib is a novel compound being developed for the treatment of various cancers.	Drug	Combination

Primary outcome

Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. bpm, beats per minute.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine)
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time)
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time
Time frame: Baseline to study completion (up to 878 days for Phase II)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine)
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time)
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time
Time frame: Baseline to study completion (up to 844 days for Phase I)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose
Time frame: Cycle 1 in Phase I (up to Day 28)
A dose-limiting toxicity (DLT) is defined as predefined adverse events or events that prevented participants from receiving 75% of their scheduled doses or from starting their next treatment period. The dose at which no more than 1 out of 6 participants experiences a DLT is defined as the optimally tolerated regimen. The OTR is important because it determines the highest dose combination that can be given without significant toxicity.
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
Time frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
Time frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
Time frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by >=50%, respectively, on consecutive scans [CS] >=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of >=25% on CS >=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as <8 w.
Progression-free Survival at 6 Months
Time frame: Date of the first dose of study drug to 6 months
Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used. The participants who are still alive and whose follow-up extends to at least 6 months are considered At Risk.

5 secondary outcomes

Phase I: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, the Time to Maximum Observed Concentration (Tmax) and C24 of Pazopanib and Lapatinib When Administered in Combination With EIAC.
Time frame: Completed during first cycle of treatment.
Phase II: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, Tmax, and C24 of Pazopanib and Lapatinib, as Appropriate, When Administered Together in Combination With Non-EIAC.
Time frame: Completed during first cycle of treatment.
Phase II: Plasma Concentrations of the Circulating Biomarkers VEGF, sVEGFR-1, and sVEGFR-2.
Time frame: Completed during first cycle of treatment.
Progression-free Survival
Time frame: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)
Time to Disease Progression or Death Due to Any Cause
Time frame: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)

Results and safety

Results posted to the registry on 20 Jun 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg	34	0
Phase II: Biomarker Positive	0	0
Phase II: Biomarker Negative	0	0

Primary outcome: Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure

Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II). Number. Unit: participants

Measure	Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg n = 33	Phase II: Biomarker Positive n = 19	Phase II: Biomarker Negative n = 22
BL, 90-<140 mmHg; shift to post-BL, 90-<140 mmgHg	21	12	11
BL, 90-<140 mmHg; shift to post-BL, 140-<170 mmHg	12	3	8
BL, 90-<140 mmHg; shift to post-BL, >=170 mmHg	0	0	1
BL, 140-<170 mmHg; shift to post-BL, 90-<140 mmHg	0	1	0
BL, 140-<170 mmHg; shift to post-BL, 140-<170 mmHg	0	2	1
BL, 140-<170 mmHg; shift to post-BL, >=170 mmHg	0	0	0
BL, >=170 mmHg; shift to post-BL, 140-<170 mmHg	0	1	1

Population analysed: All-treated Population (all participants who were given any dose of study medication) for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.

Primary outcome: Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure

Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II). Number. Unit: participants

Measure	Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg n = 33	Phase II: Biomarker Positive n = 19	Phase II: Biomarker Negative n = 22
BL, 50-<90 mmHg; shift to post-BL, 50-<90 mmHg	23	13	9
BL, 50-<90 mmHg; shift to post-BL, 90-<110 mmHg	9	4	10
BL, 90-<110 mmHg; shift to post-BL, 50-<90 mmHg	0	1	0
BL, 90-<110 mmHg; shift to post-BL, 90-<110 mmHg	1	0	2
BL, 90-<110 mmHg; shift to post-BL, >=110 mmHg	0	1	1

Population analysed: All-treated Population for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.

Primary outcome: Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate

Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II). Number. Unit: participants

Measure	Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg n = 33	Phase II: Biomarker Positive n = 19	Phase II: Biomarker Negative n = 22
BL, 44-100 bpm; shift to post-BL, 44-100 bpm	31	14	19
BL, 44-100 bpm; shift to post-BL, 101-120 bpm	0	3	2
BL, 101-120 bpm; shift to post-BL, 101-120 bpm	2	0	0
BL, 101-120 bpm; shift to post-BL, >120 bpm	0	1	0
BL, >120 bpm; shift to post-BL, 44-100 bpm	0	0	1
BL, missing; shift to post-BL, 44-100 bpm	0	1	0

Population analysed: All-treated Population for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.

Primary outcome: Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin

Time frame: Baseline to study completion (up to 878 days for Phase II). Mean (Standard Deviation). Unit: grams per liter (g/L)

Measure	Phase II: Biomarker Positive n = 19	Phase II: Biomarker Negative n = 21
Value	-5.9 (9.57)	-6.7 (9.95)

Population analysed: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and non-serious AES in Phases I and II were collected from Day 1 of study treatment to study completion (up to 844 days for Phase I; up to 878 days for Phase II).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg	15 of 34 (44.1%)	33 of 34 (97.1%)	Not reported
Phase II: Biomarker Positive	6 of 19 (31.6%)	18 of 19 (94.7%)	Not reported
Phase II: Biomarker Negative	8 of 22 (36.4%)	22 of 22 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23054212de Jonge MJ, Hamberg P, Verweij J, Savage S, Suttle AB, Hodge J, Arumugham T, Pandite LN, Hurwitz HI. Phase I and pharmacokinetic study of pazopanib and lapatinib combination therapy in patients with advanced solid tumors. Invest New Drugs. 2013 Jun;31(3):751-9. doi: 10.1007/s10637-012-9885-8. Epub 2012 Oct 6.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pazopanib and lapatinib in people with Glioma, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure (time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)). The study lists 35 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00350727, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2013.