Trial of Deforolimus in Combination With Bevacizumab for Patients With Advanced Cancers (8669-010)(COMPLETED)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, and recommended phase 2 dose of oral ridaforolimus administered in combination with intravenous bevacizumab in patients with advanced cancers.

Official Title
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A Phase I Trial of Oral Deforolimus (AP23573; MK-8669), an mTOR Inhibitor, in Combination With Bevacizumab for Patients With Advanced Cancers

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: ridaforolimus
* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Advanced or metastatic solid tumor malignancy ECOG performance status of less than or equal to 1 Life expectancy of greater than 3 months At least 4 weeks must have elapsed between prior investigational therapy, chemotherapy, or radiotherapy, and the first dose of deforolimus Adequate hematological, hepatic and renal function Serum cholesterol less than or equal to 350 mg/dL and triglycerides less than or equal to 400 mg/dL Signed informed consent Women of childbearing potential must have a negative serum pregnancy test within 7 days of starting therapy and must use an approved contraceptive method from time of screening until 30 days after the last dose of study drug Exclusion Criteria: Tumor location in close proximity to a major blood vessel History of brain metastases, spinal cord compression, or carcinomatous meningitis. Primary brain tumors (for example, glioblastoma) are allowed. New brain metastases, spinal cord compression, or leptomeningeal metastases on screening CT scan or MRI Hemoptysis or hematemesis within 28 days prior to entering the trial Clinical significant unexplained bleeding within 28 days prior to entering the trial Uncontrolled hypertension Proteinuria at screening Clinically significant cardiovascular disease Newly diagnosed or poorly controlled type 1 or 2 diabetes Active infection requiring prescribed intervention Other concurrent illness that, in the Investigator's judgement, would either compromise the patient's safety or interfere with the evaluation of the safety of the study drug Major surgery within 28 days before trial entry, or any incompletely healed surgical incision; minor surgery or procedures within 7 days Pregnant or breastfeeding Known allergy to macrolide antibiotics Known hypersensitivity to any component of bevacizumab Concurrent treatment with medications that strongly induce or inhibit cytochrome P450 (CYP3A) Known history of HIV sero-positivity Any condition in the Investigator's judgement that renders the patient unable to fully understand and provide informed consent and/or comply with the protocol

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: 1<br>30mg QDx5/wk ridaforolimus plus 10mg/kg Q2wks bevacizumab for 4 weeks | Drug: ridaforolimus<br>* oral tablets, daily for 5 days/week<br>* Other names: ridaforolimus was also known as deforolimus until May 2009;Drug: bevacizumab<br>* IV infusion<br>* Other names: avastin;|
| Experimental: 2<br>40mg QDx5/wk ridaforolimus plus 10mg/kg Q2wks bevacizumab for 4 weeks | Drug: ridaforolimus<br>* oral tablets, daily for 5 days/week<br>* Other names: ridaforolimus was also known as deforolimus until May 2009;Drug: bevacizumab<br>* IV infusion<br>* Other names: avastin;|
| Experimental: 3<br>40mg QDx5/wk ridaforolimus plus 15mg/kg Q3wks bevacizumab for 3 weeks | Drug: ridaforolimus<br>* oral tablets, daily for 5 days/week<br>* Other names: ridaforolimus was also known as deforolimus until May 2009;Drug: bevacizumab<br>* IV infusion<br>* Other names: avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of recommended phase 2 dose of ridaforolimus in combination with bevacizumab |  | Duration of the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the overall safety and tolerability of ridaforolimus in combination with bevacizumab |  | Duration of the study | 
| Description of the anti-tumor activity of ridaforolimus in combination with bevacizumab |  | Duration of the study |