Docetaxel, Gemcitabine and Pazopanib as Treatment for Soft Tissue Sarcoma

Study Overview
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Brief Summary
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Chemotherapy treatment with docetaxel and gemcitabine is a standard treatment for patients with soft tissue sarcoma. This study is designed to explore whether the addition of tyrosine kinase inhibitor pazopanib enhances the anticancer effect of the chemotherapy drugs. The Phase I component of this study is designed to determine the maximum tolerated dose of pazopanib when given with docetaxel and gemcitabine. The Phase II component is designed to determine the overall response rate of the combination of docetaxel, gemcitabine and pazopanib prior to surgical resection in patients with soft tissue sarcoma.

Official Title
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Phase I/II Study of the Combination of Docetaxel, Gemcitabine and Pazopanib for Neoadjuvant Treatment of Patients With Operable Soft Tissue Sarcoma

Conditions
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Stage III Adult Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Docetaxel
* Drug: Pazopanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older chemotherapy naive, histologically high grade soft tissue sarcoma that is considered to be operable tumor greater than 5 cm in longest dimension life expectancy of at least 6 months Zubrod performance status of 0-2 signed informed consent adequate bone marrow function defined by: absolute peripheral granulocyte count of >1500 cells/mm^3 hemoglobin >8.0 g/dl platelet count >100,000/mm^3 absence of a regular red blood cell transfusion requirement adequate hepatic function defined by: total bilirubin <1.5 x upper limit of normal (ULN) AST, ALT and alkaline phosphatase all not more than 2.5 x ULN adequate renal function defined by: 1. serum creatinine <1.5 x ULN negative pregnancy test for women of child bearing potential willingness to use effective contraception while on treatment and for 3 months thereafter Exclusion Criteria: Multiple metastases (patients with 5 or fewer oligometastases that could be resectable are eligible) Pregnant women or nursing mothers concurrent chemotherapy or radiation therapy severe medical problems (at the discretion of the investigator) history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 symptomatic brain metastases cirrhosis dermatofibrosarcoma protuberans (DFSP), embryonal rhabdomyosarcoma or alveolar soft part sarcoma (ASPS)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort 1<br> | Drug: Gemcitabine<br>* 1500 mg/m^2 given days 1 and 15 of every 28 day cycle for a total of 4 cycles<br>* Other names: Gemzar;Drug: Docetaxel<br>* 50 mg/m^2 on days 1 and 15 of each 28 day cycle for a total of 4 cycles<br>* Other names: Taxotere;Drug: Pazopanib<br>* Starting dose of 400 mg/day starting 72 hours after docetaxel/gemcitabine administration for 10 days (days 4-13 and 18-27) of each 28 day cycle for a total of 4 cycles. Dose will be increased by 200 mg/day for each cohort until the maximum tolerated dose is identified.<br>* Other names: Votrient;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | 1 cycle (28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | 4 cycles (112 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Soft tissue sarcoma, gemcitabine, docetaxel, pazopanib