SarcomaPhase 1/2NCT01418001
Gemcitabine and Docetaxel in Combination With Pazopanib (Gem/Doce/Pzb) for the Neoadjuvant Treatment of Soft Tissue Sarcoma (STS)
A Phase 1/2 study testing Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination in people with Sarcoma and Leiomyosarcoma, run by Memorial Sloan Kettering Cancer Center at 4 sites in United States.
Trial summary
The purpose of this study is to see the effects, good and/or bad, of the drug combination of gemcitabine, docetaxel and pazopanib on sarcoma. This is a phase Ib-phase II clinical trial. The goal of a phase Ib part of the clinical trial is to confirm a dose of the drugs that is safe. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma, Leiomyosarcoma, Malignant Peripheral Nerve Sheath Tumor
- What is being tested?
- Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 4 sitesUnited States
- Study dates
- Aug 2011to Nov 2015
- 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
- Patients must have histologically or cytologically confirmed extremity only, ≥8 cm, high grade STS (MPNST, MFH/UPS, LMS) at MSKCC or locally for participating sites.
- Subjects must have only localized disease that is potentially amenable to definitive resection.
- The first 15 MSKCC patients on the Phase II portion of the protocol must undergo either an open incisional or core tumor biopsy prior to the initiation of therapy.
- Patients must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10 for the evaluation of measurable disease.
- Age >18 years. ECOG performance status 0 or 1.
- Patients must have normal organ and marrow function as defined below (ULN indicates institutional upper limit of normal): Absolute neutrophil count (ANC) ≥1.5 X 109/L Hemoglobin ≥9 g/dL (5.6 mmol/L) Platelets ≥100 X 109/L International normalized ratio (INR) ≤1.2 X ULN Activated partial thromboplastin time (aPTT)≤1.2 X ULN Total bilirubin ≤1.5 X ULN Alanine amino, transferase (ALT) and Aspartate aminotransferase (AST) ≤2.5 X ULN Serum creatinine ≤1.5 mg/dL (133 μmol/L) Or, if serum creatinine, >1.5 mg/dL: Calculated creatinine clearance (ClCR)
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- ≥30 mL/min to ≥50 mL/min Urine Protein to Creatinine Ratio (UPC; appropriate appendix) <1 Or, 24-hour urine protein <1g
- Patients must not have current evidence of another malignancy.
- Pazopanib, gemcitabine and docetaxel all carry category D (positive evidence of risk) pregnancy status. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during therapy and for at least 8 weeks after completion of therapy and have pregnancy testing prior to study entry and after two cycles of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Who cannot join
- Patients who have had major surgery 4 weeks prior to entering the study, or those who have not recovered from adverse events to ≤ NCI CTC AE Grade 1, associated with surgery. Excluded from such considerations are surgical changes not expected to improve, e.g. removal of muscle tissue.
- Patients must not have had been treated previously with radiation, chemotherapy or other anti-cancer agent for the current disease.
- History of allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to pazopanib, gemcitabine, docetaxel or other agents used in the study.
- Patients with a contraindication to MRIs.
- Patients who required concomitant treatment with medications that are known to be inhibitors or strong inducers of isoenzyme CYP3A4, CYP2C8, and CYP2D6 unless the drugs are medically necessary and no substitutes are available. If there are no acceptable substitutes, special precautions should be taken in these patients. Similarly, co-administration with CYP3A inhibitors (e.g. Ergot derivatives, Neuroleptics, Antiarrhythmics, Immune modulators and miscellaneous agents such quetiapine, risperidone, clozapine, atomoxetine, and inducers (e.g. Glucocorticoids, Anticonvulsants, HIV antivirals, Antibiotics, miscellaneous agents such as St. John's Wort, modafinil, pioglitazone, troglitazone, simvastatin, should also be avoided if possible, or otherwise subject to caution (e.g. increased frequency of safety monitoring). Strong CYP3A4 inhibitors are PROHIBITED within 14 days prior to the first dose of pazopanib including: Antibiotics, HIV protease inhibitors, Antifungals and Antidepressants
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, including HIV, active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled diabetes or psychiatric illness/social situations that would limit compliance with study requirements. Hepatitis B and C will be screened for in all patients prior to initiating treatment via hepatitis B serologic markers, that is, HBsAg, HBs Ab, HBc Ab and Hep C Antibody. If patients have positive serologic markers, viral load markers (HBV-DNA and Hepatitis C RNA-PCR) will be performed during screening to confirm disease as well as screening for hepatitis C via quantitative RNA-PCR.
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- Pregnant women and women who are breast-feeding.
- HIV -positive patients on combination antiretroviral therapy due to the potential for pharmacokinetic interactions with pazopanib.
- Patients with significant respiratory compromise or an active and unexplained pneumonitis given that these patients would have an increased risk of pneumonitis from gemcitabine, and would also confuse the evaluation of pneumonitis on the trial
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- Active peptic ulcer disease
- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
- abscess within 28 days prior to beginning study treatment Active diarrhea of any grade
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
- Malabsorption syndrome
- Major resection of the stomach or small bowel
- History of any one or more of the following cardiovascular conditions within the past 6 months:
- Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
- Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible
- Corrected QT interval (QTc) ≥ 450 msecs using Bazett's formula (append formula); for subjects with bundle branch block (BBB), QTc ≥480 msecs using Bazett's formula.)
- Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg.
- Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
- History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure [see Appendix D for description]
- Evidence of active bleeding or bleeding diathesis
- Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Northwestern University
Evanston, Illinois, 60208
UCLA
Los Angeles, California, 90095
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase IB/II Study of Gemcitabine and Docetaxel in Combination With Pazopanib (Gem/Doce/Pzb) for the Neoadjuvant Treatment of Soft Tissue Sarcoma (STS)
The purpose of this study is to see the effects, good and/or bad, of the drug combination of gemcitabine, docetaxel and pazopanib on sarcoma. This is a phase Ib-phase II clinical trial. The goal of a phase Ib part of the clinical trial is to confirm a dose of the drugs that is safe. The investigators determine this by closely checking for side effects that the patient may experience.
- Conditions
- Sarcoma, Leiomyosarcoma, Malignant Peripheral Nerve Sheath Tumor, Malignant Fibrous, Histiocytoma/Undifferentiated Pleomorphic Sarcoma
- Being tested
- Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination
- Keywords
- GEMCITABINE, GW786034 (PAZOPANIB), TAXOTERE (DOCETAXEL), 11-104
- Medical subject headings
- Sarcoma, Leiomyosarcoma, Neurofibrosarcoma, Histiocytoma, Histiocytoma, Malignant Fibrous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pazopanib 400 mg QD - Gemcitabine and Docetaxel in CombinationDrug
Patients who meet the eligibility criteria above will be treated with the combination therapy of Gemcitabine, Docetaxel, and Pazopanib for two cycles and subsequently re-evaluated for treatment effect. If no progression of the tumor is seen, patients will continue with two more cycles of treatment (total four cycles). Those patients who have progression of disease will proceed directly to surgical resection.
Following completion of neoadjuvant treatment, all patients will have definitive surgical resection. Following recovery from surgery, patients will proceed with adjuvant radiation therapy. Patients will then be followed for 2 years or until January 1st 2015, whichever comes first .
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination | Experimental | This will be a multicenter single arm phase IB/II trial to evaluate the clinical safety and efficacy of gemcitabine/docetaxel and pazopanib in the neoadjuvant treatment of soft tissue sarcoma. Receives: Drug: Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Objective Response
Overall objective response measured using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Every 6 weeks up to 2 years
Secondary outcomes (1)
Pathologic Response
will be assessed by both MRI and by pathologic review after surgery. An estimate of each response rate and the 95% CI will be provided
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionNov 2015
- Study completionNov 2015
Why it stopped: Lack of accrual
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 SarcomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network, University of California, Los Angeles, Washington University School of Medicine, Northwestern University
- Responsible party
- Sponsor
- Investigators
- William Tap, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01418001
- Sponsor's protocol ID
- 11-104
- Status last verified
- Dec 2017
- First submitted
- 15 Aug 2011
- Last updated
- 11 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB/II Study of Gemcitabine and Docetaxel in Combination With Pazopanib (Gem/Doce/Pzb) for the Neoadjuvant Treatment of Soft Tissue Sarcoma (STS)
- ClinicalTrials.gov ID
- NCT01418001
- Acronym / sponsor ID
- 11-104
- Conditions
- Sarcoma, Leiomyosarcoma, Malignant Peripheral Nerve Sheath Tumor, Malignant Fibrous, Histiocytoma/Undifferentiated Pleomorphic Sarcoma
- Keywords
- GEMCITABINE, GW786034 (PAZOPANIB), TAXOTERE (DOCETAXEL), 11-104
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network, University of California, Los Angeles, Washington University School of Medicine, Northwestern University
- Study start
- Aug 2011
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 16 Aug 2011 (estimated)
- Results
- Posted 17 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see the effects, good and/or bad, of the drug combination of gemcitabine, docetaxel and pazopanib on sarcoma. This is a phase Ib-phase II clinical trial. The goal of a phase Ib part of the clinical trial is to confirm a dose of the drugs that is safe. The investigators determine this by closely checking for side effects that the patient may experience.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination | Experimental | Drug: Pazopanib 400 mg QD - Gemcitabine and Docetaxel in CombinationThis will be a multicenter single arm phase IB/II trial to evaluate the clinical safety and efficacy of gemcitabine/docetaxel and pazopanib in the neoadjuvant treatment of soft tissue sarcoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must have histologically or cytologically confirmed extremity only, ≥8 cm, high grade STS (MPNST, MFH/UPS, LMS) at MSKCC or locally for participating sites.
- Subjects must have only localized disease that is potentially amenable to definitive resection.
- The first 15 MSKCC patients on the Phase II portion of the protocol must undergo either an open incisional or core tumor biopsy prior to the initiation of therapy.
- Patients must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10 for the evaluation of measurable disease.
- Age >18 years. ECOG performance status 0 or 1.
Key exclusion criteria (27 listed)
- Patients who have had major surgery 4 weeks prior to entering the study, or those who have not recovered from adverse events to ≤ NCI CTC AE Grade 1, associated with surgery. Excluded from such considerations are surgical changes not expected to improve, e.g. removal of muscle tissue.
- Patients must not have had been treated previously with radiation, chemotherapy or other anti-cancer agent for the current disease.
- History of allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to pazopanib, gemcitabine, docetaxel or other agents used in the study.
- Patients with a contraindication to MRIs.
- Patients who required concomitant treatment with medications that are known to be inhibitors or strong inducers of isoenzyme CYP3A4, CYP2C8, and CYP2D6 unless the drugs are medically necessary and no substitutes are available. If there are no acceptable substitutes, special precautions should be taken in these patients. Similarly, co-administration with CYP3A inhibitors (e.g. Ergot derivatives, Neuroleptics, Antiarrhythmics, Immune modulators and miscellaneous agents such quetiapine, risperidone, clozapine, atomoxetine, and inducers (e.g. Glucocorticoids, Anticonvulsants, HIV antivirals, Antibiotics, miscellaneous agents such as St. John's Wort, modafinil, pioglitazone, troglitazone, simvastatin, should also be avoided if possible, or otherwise subject to caution (e.g. increased frequency of safety monitoring). Strong CYP3A4 inhibitors are PROHIBITED within 14 days prior to the first dose of pazopanib including: Antibiotics, HIV protease inhibitors, Antifungals and Antidepressants
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 |
|---|---|---|
| Pazopanib 400 mg QD - Gemcitabine and Docetaxel in CombinationPatients who meet the eligibility criteria above will be treated with the combination therapy of Gemcitabine, Docetaxel, and Pazopanib for two cycles and subsequently re-evaluated for treatment effect. If no progression of the tumor is seen, patients will continue with two more cycles of treatment (total four cycles). Those patients who have progression of disease will proceed directly to surgical resection. Following completion of neoadjuvant treatment, all patients will have definitive surgical resection. Following recovery from surgery, patients will proceed with adjuvant radiation therapy. Patients will then be followed for 2 years or until January 1st 2015, whichever comes first . | Drug | Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination |
Primary outcome
Overall Objective Response
Time frame: Every 6 weeks up to 2 years
Overall objective response measured using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
1 secondary outcome
Pathologic Response
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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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.
William Tap, MD principal investigator
Memorial Sloan Kettering Cancer Center
4 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 Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination in people with Sarcoma and Leiomyosarcoma, run by Memorial Sloan Kettering Cancer Center at 4 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 9 inclusion and 27 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: stopped early, as of the sponsor's last update on 11 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 17 Feb 2016). 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?
Overall Objective Response (time frame: Every 6 weeks up to 2 years). 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 11 Jan 2018.