Adult Giant Cell GlioblastomaPhase 1/2NCT00335764
Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
A Phase 1/2 study testing sorafenib tosylate, erlotinib hydrochloride and tipifarnib in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 7 sites in United States.
Trial summary
This phase I/II trial is studying the side effects and best dose of erlotinib, tipifarnib, and temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- sorafenib tosylate, erlotinib hydrochloride and tipifarnib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 7 sitesUnited States
- Study dates
- Apr 2006to Sep 2012
- Phase
- Phase 1/2
- 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
- Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma
- Evidence of tumor progression by MRI or CT scan within the past 14 days AND on a steroid dose that has been stable for ≥ 5 days
- Patients who underwent prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by either positron emission tomography or thallium scanning, magnetic resonance (MR) spectroscopy, or surgical documentation of disease
- Recent resection of recurrent or progressive tumor allowed
- Residual disease is not required
- Treatment for any number of prior relapses, defined as disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial treatment), allowed (phase I)
Show all 57Show fewer
- No more than 3 prior therapies (initial therapy and therapy for 2 relapses) (phase II)
- Each of the following is considered 1 relapse:
- Disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial therapy)
- Underwent a surgical resection for relapsed disease and received no anticancer therapy for up to 12 weeks after surgical resection AND then underwent a subsequent surgical resection
- Received prior therapy for a low-grade glioma, followed by a surgical diagnosis of glioblastoma
- Failed prior radiotherapy
- 15 unstained paraffin slides or 1 tissue block must be available from original surgery, definitive surgery, or surgery closest to the initiation of this study (phase II)
- Karnofsky performance status 60-100%
- White Blood Cell (WBC) ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL (transfusion allowed)
- Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN)
- Total bilirubin normal
- Creatinine < 1.5 mg/dL
- Prothrombin time (PT)/ international normalized ratio (INR) ≤ 1.5 (INR < 3.0 for patients on anticoagulation therapy)
- INR < 1.1 times upper limit of normal (ULN) (for patients on prophylactic anticoagulation therapy [low-dose warfarin])
- Fasting cholesterol < 350 mg/dL (for patients receiving temsirolimus and sorafenib)
- Fasting triglycerides < 400 mg/dL (for patients receiving temsirolimus and sorafenib)
- Well-controlled hypertension (e.g., systolic blood pressure ≤ 140 mm Hg or diastolic pressure ≤ 90 mm Hg) allowed
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for at least 2 weeks (women) or 3 months (men) after completion of study treatment
- No peripheral neuropathy > grade 1 (for patients receiving sorafenib and tipifarnib)
- No evidence of bleeding diathesis or coagulopathy
- No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for ≥ 3 years
- No significant traumatic injury within the past 21 days
- No active infection or serious medical illness that would preclude study treatment
- No condition that would impair ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation or active peptic ulcer disease)
- No HIV disease
- No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole or econazole) or a history of allergic reactions attributed to any compound of similar chemical or biological composition to tipifarnib (for patients receiving sorafenib and tipifarnib)
- No other disease that would obscure toxicity or dangerously alter drug metabolism
- Recovered from prior therapy
- At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) (radiosensitizer does not count)
- At least 14 days since prior vincristine
- At least 21 days since prior procarbazine or major surgery
- At least 28 days since prior investigational agent or cytotoxic therapy
- At least 42 days since prior nitrosoureas or radiotherapy
- No prior sorafenib, AEE788, or vatalanib
- No prior surgical procedures affecting absorption
- No prior tipifarnib, lonafarnib, or other agents targeting farnesyl transferase (for patients receiving sorafenib and tipifarnib)
- No prior temsirolimus or mechanistic target of rapamycin (mTOR-targeting agent) (phase II), rapamycin or everolimus, or Akt-pathway inhibitors (for patients receiving sorafenib and temsirolimus)
- No prior erlotinib hydrochloride, multitargeted human epidermal receptor (AEE788), or other epidermal growth factor receptor targeting agents (phase II) (for patients receiving sorafenib and erlotinib hydrochloride)
- No concurrent enzyme-inducing antiepileptic drugs (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, or primidone)
- Dexamethasone allowed
- No concurrent hepatic cytochrome p450 enzyme-inducing anticonvulsants
- No other concurrent investigational agents or anticancer therapies, including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy
- No concurrent prophylactic filgrastim (G-CSF) or other hematopoietic colony-stimulating factors
- Full-dose anticoagulants allowed provided both of the following criteria are met:
- In-range INR (between 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
Who cannot join
None listed.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
M D Anderson Cancer Center
Houston, Texas, 77030
University of California at Los Angeles
Los Angeles, California, 90095
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
University of Pittsburgh
Pittsburgh, Pennsylvania, 15232
University of California San Francisco
San Francisco, California, 94115
About this study
Official title: Phase I/II Studies of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib), R115777 (Tipifarnib) or CCI-779 (Temsirolimus) in Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
This phase I/II trial is studying the side effects and best dose of erlotinib, tipifarnib, and temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Sorafenib, erlotinib, tipifarnib, and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib and tipifarnib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib, tipifarnib, or temsirolimus may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
Phase 1
- Determine the maximum tolerated dose (MTD) of tipifarnib, erlotinib hydrochloride, or temsirolimus in combination with a fixed dose of sorafenib in patients with recurrent glioblastoma multiforme or gliosarcoma who are not taking enzyme-inducing antiepileptic drugs.
SECONDARY OBJECTIVES:
Phase 1 and 2
- Characterize the safety profile of the doublet combinations of tipifarnib-sorafenib, erlotinib hydrochloride-sorafenib, and temsirolimus-sorafenib in patients with recurrent glioblastoma multiforme or gliosarcoma.
- Characterize the pharmacokinetics of these doublet combinations, evaluating single-agent pharmacokinetics of each agent and the combination pharmacokinetics to determine drug-drug interactions.
Phase 2
- Determine the efficacy of each of the doublet combinations, in terms of 6-month progression-free survival, in patients with recurrent glioblastoma multiforme or gliosarcoma.
- Determine the efficacy of each of the doublet combinations, in terms of 12-month survival and objective tumor response, in patients with recurrent glioblastoma multiforme or gliosarcoma.
TERTIARY OBJECTIVES:
Phase 2
- Perform exploratory correlative laboratory studies by examining tissue markers of signal transduction pathways by immunohistochemical analysis using tissue blocks obtained prior to initiation of protocol therapy, either from the time of diagnosis or subsequent tumor resection.
- Determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents.
OUTLINE:
This is a multicenter, phase I, dose-escalation study of tipifarnib, erlotinib hydrochloride, and temsirolimus followed by a phase II open-label study.
PHASE I:
Patients are sequentially assigned to 1 of 3 treatment groups.
GROUP 1: Patients receive oral sorafenib twice daily and oral erlotinib hydrochloride once daily on days 1-28.
GROUP 2: Patients receive sorafenib as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
GROUP 3: Patients receive sorafenib as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21.
In all groups, treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
In each treatment group, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride (group 1), temsirolimus (group 2), or tipifarnib (group 3) sequentially until the maximum tolerated dose (MTD) is determined for each group. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.
PHASE II:
Patients receive sorafenib as in phase I. Patients also receive erlotinib hydrochloride, temsirolimus, or tipifarnib as in phase I at the MTD determined in phase I.
Tissue that was collected during a prior surgery is examined for biomarkers by immunohistochemistry (in patients enrolled in the phase II portion of the study). Biomarkers examined include epidermal growth factor receptor, Receptor tyrosine-protein kinase (HER-2), Protein kinase B (AKT), S6 ribosomal protein, and Receptor-linked tyrosine kinases (Erk).
After completion of study treatment, patients are followed every 3 months.
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Being tested
- sorafenib tosylate, erlotinib hydrochloride, tipifarnib, temsirolimus
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenib tosylateDrug
Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar
given orally
erlotinib hydrochlorideDrug
Also called CP-358,774, erlotinib, OSI-774
given orally
tipifarnibDrug
Also called R115777, Zarnestra
given orally
temsirolimusDrug
Also called CCI-779, cell cycle inhibitor 779, Torisel
IV administration
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28. Receives: Drug: sorafenib tosylate; Drug: erlotinib hydrochloride |
| Group 2 | Experimental | Patients receive sorafenib tosylate as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Receives: Drug: sorafenib tosylate; Drug: temsirolimus |
| Group 3 | Experimental | Patients receive sorafenib tosylate as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21. Receives: Drug: sorafenib tosylate; Drug: tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of the Each Combination Agent Combined With a Fixed Dose of BAY 43-9006 Determined by Dose-limiting Toxicities (DLT) (Phase I)
DLT defined as: any grade 4 hematologic toxicity; grade 3 thrombocytopenia > 7 days, any grade 3/4 non-hematologic toxicity (despite maximal medical therapy), any intolerable grade 2 non-hematological, ro grade 3 hematological toxicity requiring deduction during first 28 days of treatment, any toxicity resulting in delay of >1week during first 28 days of treatment
Measured: 28 days
Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Group 2: 13 patients received temsirolimus 25mg IV and 7 patients treated with 200mg Sorafenib and 6 patients treated with 400mg Sorafenib
Measured: cycle 1 ((Day1, Day15, Day28)
Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
8 samples collected over 24 hours on Day 1, day 15 and day 28
13 total patients treated 100mg Erlotinib and either 200mg or 400mg of Sorafenib
Measured: 28days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration)
Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
8 samples collected over 24 hours on Day 1, day 15 and day 28
16 patients Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference AUC - Area Under Curve
Measured: 28Days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration) AUC 0-12
Trough Concentration Group 2 Sorafenib and Temsirolimus (Phase I)
Group 2: 12 patients were analyzed for Day 1 (1 patient not evaluable), 5 patients were analyzed for Day 15 (8 patients not evaluable)
Measured: 15 days
Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
Day 1 = 12 patients (1 sample not evaluable) Day 15 = 5 patients (8 samples not evaluable)
AUC - Area Under Curve
8 samples collected over 24 hours - 28 day PKs
Measured: Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)
Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Group 3: Only PKs for Dose level 1 and -1 were collected.
Measured: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Group 3: patients were studied for their day 1 Cmax, and day 15 Cmax Tipifanib and Day 15 and Day 28 sorafenib
Group 3: Only PKs for Dose level 1 and -1 were collected.
Measured: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
Group 3: PKs for Dose level -1 100mg QD
Note that although 9 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Measured: Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
Group 3: PKs for Dose level 1 Tipifarnib 100mg BID
Measured: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
12 Month Survival Rate (Phase II)
number of patients alive at 12 months
Measured: 12 months
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
CTCAE 3.0
Measured: 28 days
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Measured: 1 year
Progression-free Survival at 6 Months (Phase II)
Patients with a scan at 6 months without progressive disease Progressive disease defined as Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.
Measured: 6 months
Objective Response Rate in Patients With Measurable Disease (Phase II)
Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined.
Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids.
Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone.
Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2006 (estimated)
- Study startApr 2006
- Primary completionFeb 2010
- Study completionSep 2012
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.
- Other trials for Adult Giant Cell GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Gilbert, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00335764
- Sponsor's protocol ID
- NCI-2009-00676
- Other IDs
- NCI-2009-00676, CDR0000476286, NABTC-05-02, NABTC-05-02, U01CA137443
- Status last verified
- May 2018
- First submitted
- 8 Jun 2006
- Last updated
- 2 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Studies of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib), R115777 (Tipifarnib) or CCI-779 (Temsirolimus) in Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
- ClinicalTrials.gov ID
- NCT00335764
- Acronym / sponsor ID
- NCI-2009-00676
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2006
- Primary completion
- Feb 2010 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 12 Jun 2006 (estimated)
- Results
- Posted 2 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial is studying the side effects and best dose of erlotinib, tipifarnib, and temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Sorafenib, erlotinib, tipifarnib, and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib and tipifarnib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib, tipifarnib, or temsirolimus may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
Phase 1
- Determine the maximum tolerated dose (MTD) of tipifarnib, erlotinib hydrochloride, or temsirolimus in combination with a fixed dose of sorafenib in patients with recurrent glioblastoma multiforme or gliosarcoma who are not taking enzyme-inducing antiepileptic drugs.
SECONDARY OBJECTIVES:
Phase 1 and 2
- Characterize the safety profile of the doublet combinations of tipifarnib-sorafenib, erlotinib hydrochloride-sorafenib, and temsirolimus-sorafenib in patients with recurrent glioblastoma multiforme or gliosarcoma.
- Characterize the pharmacokinetics of these doublet combinations, evaluating single-agent pharmacokinetics of each agent and the combination pharmacokinetics to determine drug-drug interactions.
Phase 2
- Determine the efficacy of each of the doublet combinations, in terms of 6-month progression-free survival, in patients with recurrent glioblastoma multiforme or gliosarcoma.
- Determine the efficacy of each of the doublet combinations, in terms of 12-month survival and objective tumor response, in patients with recurrent glioblastoma multiforme or gliosarcoma.
TERTIARY OBJECTIVES:
Phase 2
- Perform exploratory correlative laboratory studies by examining tissue markers of signal transduction pathways by immunohistochemical analysis using tissue blocks obtained prior to initiation of protocol therapy, either from the time of diagnosis or subsequent tumor resection.
- Determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents.
OUTLINE:
This is a multicenter, phase I, dose-escalation study of tipifarnib, erlotinib hydrochloride, and temsirolimus followed by a phase II open-label study.
PHASE I:
Patients are sequentially assigned to 1 of 3 treatment groups.
GROUP 1: Patients receive oral sorafenib twice daily and oral erlotinib hydrochloride once daily on days 1-28.
GROUP 2: Patients receive sorafenib as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
GROUP 3: Patients receive sorafenib as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21.
In all groups, treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
In each treatment group, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride (group 1), temsirolimus (group 2), or tipifarnib (group 3) sequentially until the maximum tolerated dose (MTD) is determined for each group. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.
PHASE II:
Patients receive sorafenib as in phase I. Patients also receive erlotinib hydrochloride, temsirolimus, or tipifarnib as in phase I at the MTD determined in phase I.
Tissue that was collected during a prior surgery is examined for biomarkers by immunohistochemistry (in patients enrolled in the phase II portion of the study). Biomarkers examined include epidermal growth factor receptor, Receptor tyrosine-protein kinase (HER-2), Protein kinase B (AKT), S6 ribosomal protein, and Receptor-linked tyrosine kinases (Erk).
After completion of study treatment, patients are followed every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: sorafenib tosylate, Drug: erlotinib hydrochloridePatients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28. |
| Group 2 | Experimental | Drug: sorafenib tosylate, Drug: temsirolimusPatients receive sorafenib tosylate as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. |
| Group 3 | Experimental | Drug: sorafenib tosylate, Drug: tipifarnibPatients receive sorafenib tosylate as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (57 listed)
- Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma
- Evidence of tumor progression by MRI or CT scan within the past 14 days AND on a steroid dose that has been stable for ≥ 5 days
- Patients who underwent prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by either positron emission tomography or thallium scanning, magnetic resonance (MR) spectroscopy, or surgical documentation of disease
- Recent resection of recurrent or progressive tumor allowed
- Residual disease is not required
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| sorafenib tosylateAlso: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavargiven orally | Drug | Group 1, Group 2, Group 3 |
| erlotinib hydrochlorideAlso: CP-358,774, erlotinib, OSI-774given orally | Drug | Group 1 |
| tipifarnibAlso: R115777, Zarnestragiven orally | Drug | Group 3 |
| temsirolimusAlso: CCI-779, cell cycle inhibitor 779, ToriselIV administration | Drug | Group 2 |
Primary outcome
Maximum Tolerated Dose (MTD) of the Each Combination Agent Combined With a Fixed Dose of BAY 43-9006 Determined by Dose-limiting Toxicities (DLT) (Phase I)
Time frame: 28 days
DLT defined as: any grade 4 hematologic toxicity; grade 3 thrombocytopenia > 7 days, any grade 3/4 non-hematologic toxicity (despite maximal medical therapy), any intolerable grade 2 non-hematological, ro grade 3 hematological toxicity requiring deduction during first 28 days of treatment, any toxicity resulting in delay of >1week during first 28 days of treatment
Pharmacokinetic Max Concentration (Cmax) of Group 2 Sorafenib and Temsirolimus (Phase I)
Time frame: cycle 1 ((Day1, Day15, Day28)
Group 2: 13 patients received temsirolimus 25mg IV and 7 patients treated with 200mg Sorafenib and 6 patients treated with 400mg Sorafenib
Pharmacokinetic cMax Group 1 Sorafenib and Erlotinib (Phase I)
Time frame: 28days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration)
8 samples collected over 24 hours on Day 1, day 15 and day 28 13 total patients treated 100mg Erlotinib and either 200mg or 400mg of Sorafenib
Pharmacokinetic AUC 0-12 Group 1 Sorafenib and Erlotinib (Phase I)
Time frame: 28Days (D1, D15, D28) (0,1,2,4,6,8,12,24hr post administration) AUC 0-12
8 samples collected over 24 hours on Day 1, day 15 and day 28 16 patients Note that although 16 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference AUC - Area Under Curve
Trough Concentration Group 2 Sorafenib and Temsirolimus (Phase I)
Time frame: 15 days
Group 2: 12 patients were analyzed for Day 1 (1 patient not evaluable), 5 patients were analyzed for Day 15 (8 patients not evaluable)
Plasma Time Curve (AUC) of Group 2 Sorafenib and Temsirolimus (Phase I)
Time frame: Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)
Day 1 = 12 patients (1 sample not evaluable) Day 15 = 5 patients (8 samples not evaluable) AUC - Area Under Curve 8 samples collected over 24 hours - 28 day PKs
Pharmacokinetic Cpmax Group 3 Sorafenib and Tipifarnib (Phase I) 100 mg QD (Level -1)
Time frame: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Group 3: Only PKs for Dose level 1 and -1 were collected.
Pharmacokinetic CpMax Concentration of Group 3 Sorafenib and Tipifarnib (Phase I) 100mg BID
Time frame: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Group 3: patients were studied for their day 1 Cmax, and day 15 Cmax Tipifanib and Day 15 and Day 28 sorafenib Group 3: Only PKs for Dose level 1 and -1 were collected.
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg QD (Level -1)
Time frame: Cycle 1 (D1, D15, D28) (0,1,2,4,6,8,12,24hr post drug administration)
Group 3: PKs for Dose level -1 100mg QD Note that although 9 patients were accrued/analyzed some samples were incomplete or inevaluable or missing hence number analyzed difference
Plasma Time Curve (AUC) of Group 3 Phase I Sorafenib and Tipifarnib 100mg BID (Level 1)
Time frame: Cycle 1 = 28 day PKs D1, D15,D28 (0,1,2,4,6,8,12,24hr post drug administration)
Group 3: PKs for Dose level 1 Tipifarnib 100mg BID
12 Month Survival Rate (Phase II)
Time frame: 12 months
number of patients alive at 12 months
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase I)
Time frame: 28 days
CTCAE 3.0
Number of High Grade (3 and 4) Related Adverse Events of Each Combination Agent Combined With BAY 43-9006 (Phase 2)
Time frame: 1 year
Progression-free Survival at 6 Months (Phase II)
Time frame: 6 months
Patients with a scan at 6 months without progressive disease Progressive disease defined as Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.
Objective Response Rate in Patients With Measurable Disease (Phase II)
Time frame: Up to 5 years
Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Adult Giant Cell Glioblastoma
Active, not recruitingPhase 1
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Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma
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.
Mark Gilbert, MD principal investigator
National Cancer Institute (NCI)
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing sorafenib tosylate, erlotinib hydrochloride and tipifarnib in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 7 sites in United States.
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 57 inclusion and 0 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 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 2 Jul 2018). 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?
Maximum Tolerated Dose (MTD) of the Each Combination Agent Combined With a Fixed Dose of BAY 43-9006 Determined by Dose-limiting Toxicities (DLT) (Phase I) (time frame: 28 days). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Jul 2018.