Gemcitabine and Docetaxel in Combination With Pazopanib (Gem/Doce/Pzb) for the Neoadjuvant Treatment of Soft Tissue Sarcoma (STS)

NCT01418001 | Terminated Phase 1 Results

• 1 other identifier: 11-104
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief 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. 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

Keywords

GEMCITABINE; GW786034 (PAZOPANIB); TAXOTERE (DOCETAXEL); 11-104

Outcome Measures

Primary Outcomes (1)

• 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.

  Every 6 weeks up to 2 years

Secondary Outcomes (1)

• Pathologic Response

  2 years

Study Arms (1)

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.

Drug: Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination

Interventions

Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination DRUG

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 .

Pazopanib 400 mg QD - Gemcitabine and Docetaxel in Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• ≥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.

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Comprehensive Cancer Network: collaborator
• University of California, Los Angeles: collaborator
• Washington University School of Medicine: collaborator
• Northwestern University: collaborator

Study Sites (4)

UCLA

Los Angeles, California, 90095, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Sarcoma; Leiomyosarcoma; Neurofibrosarcoma; Histiocytoma; Histiocytoma, Malignant Fibrous

Interventions

pazopanib; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. William Tap
• Organization: Memorial Sloan Kettering Cancer Center

tapw@mskcc.org

646-888-4163

Study Officials

• William Tap, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2011
• First Posted: August 16, 2011
• Study Start: August 1, 2011
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: January 11, 2018
• Results First Posted: February 17, 2016

Record last verified: 2017-12

Locations

US (4)