Phase IB Study of Gemcitabine, Docetaxel and Bevacizumab in Patients With Soft Tissue Sarcoma

Study Overview
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Brief Summary
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1.1 To determine the recommended phase II dose for gemcitabine in combination with a fixed dose of docetaxel and bevacizumab. 1.2 To determine the efficacy of the combination of gemcitabine, docetaxel, and bevacizumab in patients with soft tissue sarcoma 1.3 To determine the toxicity profile of the combination of gemcitabine, docetaxel, and bevacizumab in patients with soft tissue sarcoma

Detailed Description
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Because the combination of gemcitabine and docetaxel has shown impressive activity in soft tissue sarcoma, we hypothesize that the addition of an antiangiogenesis agent (bevacizumab) would enhance the anticancer activity, as shown in other tumor types.

Official Title
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Phase IB Study of Gemcitabine, Docetaxel and Bevacizumab in Patients With Soft Tissue Sarcoma

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: Gemcitabine, Docetaxel and Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: All patients, 18 years of age or older, with chemotherapy naive soft tissue sarcoma are eligible if there is measurable disease Prior surgery or radiotherapy for the primary tumor is allowed but needs to have been completed at least 2 weeks from entry, and patient should have completely recovered from the procedures. Patients must have a life expectancy of at least 12 weeks. Patients must have a Zubrod performance status of 0-2. Patients must sign an informed consent. Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of > 1,500 or cells/mm3 and platelet count >100,000/mm3 and absence of a regular red blood cell transfusion requirement. Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine < 1.5 x upper limit of normal. Exclusion Criteria: Patients with symptomatic brain metastases are excluded from this study. Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. Patients may receive no other concurrent chemotherapy or radiation therapy during this trial. Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>1000mg/m2 gemcitabine | Drug: Gemcitabine, Docetaxel and Bevacizumab<br>* During the treatment phase, pts. will receive the drug combination of gemcitabine, docetaxel, and bevacizumab every 2 weeks for a period of 4 weeks. This 4-week period is called a cycle of treatment. The treatment consists of receiving docetaxel IV over a 60-minute period and gemcitabine IV over a 30-minute period. Pts. will then receive bevacizumab IV over a 30-minute period. Pts. will receive this treatment once every 2 weeks. Pts. will receive at least 2 cycles of treatment unless you have progression of your disease or unmanageable side effects. As long as the size of pts.'s tumor stays the same or gets smaller, pts may continue receiving treatment<br>* Other names: Avastin;|
| Experimental: Cohort 2<br>1250 mg/m2 gemcitabine | Drug: Gemcitabine, Docetaxel and Bevacizumab<br>* During the treatment phase, pts. will receive the drug combination of gemcitabine, docetaxel, and bevacizumab every 2 weeks for a period of 4 weeks. This 4-week period is called a cycle of treatment. The treatment consists of receiving docetaxel IV over a 60-minute period and gemcitabine IV over a 30-minute period. Pts. will then receive bevacizumab IV over a 30-minute period. Pts. will receive this treatment once every 2 weeks. Pts. will receive at least 2 cycles of treatment unless you have progression of your disease or unmanageable side effects. As long as the size of pts.'s tumor stays the same or gets smaller, pts may continue receiving treatment<br>* Other names: Avastin;|
| Experimental: Cohort 3<br>1500 mg/m2 gemcitabine | Drug: Gemcitabine, Docetaxel and Bevacizumab<br>* During the treatment phase, pts. will receive the drug combination of gemcitabine, docetaxel, and bevacizumab every 2 weeks for a period of 4 weeks. This 4-week period is called a cycle of treatment. The treatment consists of receiving docetaxel IV over a 60-minute period and gemcitabine IV over a 30-minute period. Pts. will then receive bevacizumab IV over a 30-minute period. Pts. will receive this treatment once every 2 weeks. Pts. will receive at least 2 cycles of treatment unless you have progression of your disease or unmanageable side effects. As long as the size of pts.'s tumor stays the same or gets smaller, pts may continue receiving treatment<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (complete and partial responses). | Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). ORR is the sum of the percentages of patients achieving complete and partial responses | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Soft Tissue Sarcoma, Phase I, Gemcitabine, Docetaxel, Bevacizumab, vascular endothelial growth factor