Ascending Multiple-Dose Study of Brivanib Alaninate in Combination With Chemotherapeutic Agents in Subjects With Advanced Cancers

Study Overview
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Brief Summary
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To determine safety and maximum tolerated dose of brivanib alaninate when administered in combination with capecitabine, doxorubicin, ixabepilone, docetaxel and paclitaxel chemotherapy to subjects with advanced or metastatic solid tumors

Official Title
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A Phase I, Multi-arm, Dose Escalation Study of Brivanib Alaninate Combined With Several Chemotherapy Regimens in Subjects With Solid Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Doxorubicin
* Drug: Ixabepilone
* Drug: Docetaxel
* Drug: Paclitaxel
* Drug: Brivanib alaninate


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Histologic/cytologic diagnosis of advanced or metastatic solid tumors Life expectancy >= 3 months Able to swallow tablets/capsules Exclusion Criteria: Pregnant or breastfeeding women No more than 4 previous chemotherapy regimens in the advanced or metastatic setting (excluding prior adjuvant or hormonal / immuno / biologic antibody therapies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Capecitabine + Brivanib alaninate)<br> | Drug: Capecitabine<br>* Tablets, Oral, Dose escalation to a MTD from a starting dose of 850 mg/m², twice a day (BID) x 14d per cycle, until disease progression<br>* Other names: Xleoda®;Drug: Brivanib alaninate<br>* Tablets, Oral, Dose escalation to a MTD from a starting dose of 400 mg, daily (QD), until disease progression<br>* Other names: BMS-540215;|
| Experimental: Arm B (Doxorubicin + Brivanib alaninate)<br> | Drug: Doxorubicin<br>* IV, Dose escalation to a MTD from a starting dose of 40 mg/m², Q3wks, until disease progression<br>* Other names: Adriamycin®;Drug: Brivanib alaninate<br>* Tablets, Oral, Dose escalation to a MTD from a starting dose of 400 mg, daily (QD), until disease progression<br>* Other names: BMS-540215;|
| Experimental: Arm C (Ixabepilone + Brivanib alaninate)<br> | Drug: Ixabepilone<br>* IV, Dose Escalation to a MTD from a starting dose of 32 mg/m², Q3wks, until disease progression<br>* Other names: BMS-247550;Drug: Brivanib alaninate<br>* Tablets, Oral, Dose escalation to a MTD from a starting dose of 400 mg, daily (QD), until disease progression<br>* Other names: BMS-540215;|
| Experimental: Arm D (Docetaxel + Brivanib alaninate)<br> | Drug: Docetaxel<br>* IV, Dose escalation to an MTD from a starting dose of 60 mg/m², Q3wks, Until disease progression<br>* Other names: Taxotere®;Drug: Brivanib alaninate<br>* Tablets, Oral, Dose escalation to a MTD from a starting dose of 400 mg, daily (QD), until disease progression<br>* Other names: BMS-540215;|
| Experimental: Arm E (Paclitaxel + Brivanib alaninate)<br> | Drug: Paclitaxel<br>* IV, Dose escalation to an MTD from a starting dose of Paclitaxel 135 mg/m², Q3wks, Until disease progression<br>* Other names: Taxol®;Drug: Brivanib alaninate<br>* Tablets, Oral, Dose escalation to a MTD from a starting dose of 400 mg, daily (QD), until disease progression<br>* Other names: BMS-540215;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine safety and the maximum tolerated dose of brivanib alaninate when administered in combination with capecitabine, doxorubicin, ixabepilone, docetaxel and paclitaxel chemotherapy to subjects with advanced or metastatic solid tumors |  | Every 21 days until the maximum tolerated dose (MTD) for each combination of brivanib is reached | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe the anti-tumor activity of brivanib alaninate combination with the different chemotherapeutic regimens: capecitabine, doxorubicin, ixabepilone, docetaxel, and paclitaxel |  | Every 21 days | 
| To assess the effect each of capecitabine, doxorubicin, ixabepilone, docetaxel, and paclitaxel on the pharmacokinetics of BMS-540215 (active moiety of brivanib pro-drug) at the MTD |  | Cycle 1D21, Days 1, 2, 3, 8 of Cycles 1 & 2 | 
| To assess the effect of brivanib alaninate on the pharmacokinetics each of capecitabine, doxorubicin, ixabepilone, docetaxel, and paclitaxel chemotherapy regimens at the MTD |  | Cycle 1D21, Days 1, 2, 3, 8 of Cycles 1 & 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, chemotherapy combination