Sorafenib and Bevacizumab in Combination With Paclitaxel in Patients With Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability and describe the maximum tolerated dose (MTD) of treatment with escalating doses of sorafenib in combination with bevacizumab and paclitaxel for patients with advanced solid tumors.

Official Title
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Phase I Dose-Escalation Drug-Interaction Study of Sorafenib and Bevacizumab in Combination With Paclitaxel in Patients With Solid Tumors

Conditions
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SOLID TUMORS

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of a solid tumor with evidence of residual, recurrent, or metastatic disease. Patients must be incurable by surgical or other standard available therapy Measurable or evaluable disease; tumor size of ≥ 2 cm on CT scan Patients may have received prior standard taxane therapy or anti-VEGF therapy, but may not have progressed on both therapies. Progression on one type therapy (either taxane or anti-VEGF) is allowed Exclusion Criteria: History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis). Prior chemotherapy ≤ 3 weeks prior to registration. Patients must have recovered from all therapy-related toxicities Prior biologic or immunotherapy ≤ 3 weeks prior to registration. Patients must have recovered from all therapy-related toxicities Prior full pelvic field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered to less than or equal to grade 1 from all therapy-related toxicities except alopecia. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of evaluable disease Major surgery (i.e., laparotomy) ≤ 4 weeks prior to randomization or anticipation of need for major surgical procedure during the course of the study Minor surgery ≤ 2 weeks prior to randomization. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities Peripheral neuropathy with functional impairment ≥ Common Terminology Criteria (CTC) grade 2 neuropathy, regardless of causality Pleural effusion or ascites that causes respiratory compromise (≥ CTC grade 2 dyspnea) Concurrent severe and/or uncontrolled cardiac, vascular or infectious conditions (as described in the protocol) which could compromise participation in the study Patients at risk of QT prolongation such as patients with congenital long QT syndrome or with long corrected QT (QTc) at baseline (i.e. QTc greater than 450 msec in males, and greater than 470 msec in females) will be excluded Lung carcinoma of squamous cell histology (mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is not acceptable).

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: Sorafenib, Bevacizumab & Paclitaxel<br>Paclitaxel is given as i.v infusion over 60 min on days 1, 8, 15 every 28 days. Sorafenib is given orally starting with cycle 1 day 2. Bevacizumab is given as i.v infusion on days 1 and 15 every 28 days. | Drug: Sorafenib<br>* Cohort 1 200 mg po BID D1-5; Cohort 2 200 mg po BID; Cohort 3 400 mg po BID D1-5 Cohort 4 400 mg po BID<br>* Other names: Bay 43-9006;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability and describe the maximum tolerated dose (MTD) of treatment with escalating doses of sorafenib in combination with bevacizumab and paclitaxel for patients with advanced solid tumors. |  | baseline through end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pharmacokinetics of paclitaxel and sorafenib alone and in combination |  | baseline through end of treatment | 
| To evaluate pharmacodynamic changes a)in tumor vascular parameters and b)in plasma VEGF and soluble VEGF receptor levels, and correlate with clinical outcomes and sorafenib pharmacokinetic (PK) profile. |  | baseline through end of treatment | 
| To evaluate variants in genes of paclitaxel drug-metabolism and drug-transporters P glycoprotein and correlate with PK profile for paclitaxel and with clinical outcomes |  | baseline through end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumor