A Study of PRO95780 Administered in Combination With the FOLFOX Regimen and Bevacizumab in Patients With Previously Untreated, Locally Advanced, Recurrent, and Metastatic Colorectal Cancer (APM4566g)

Study Overview
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Brief Summary
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This will be a multicenter, open-label study enrolling a total of up to 23 patients.

Official Title
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A Phase Ib Study of the Safety and Pharmacokinetics of PRO95780 Administered in Combination With the FOLFOX Regimen and Bevacizumab in Patients With Previously Untreated, Locally Advanced, Recurrent, and Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab
* Drug: FOLFOX
* Drug: PRO95780


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed CRC with evidence of locally advanced recurrent or metastatic disease and measurable tumor lesions Life expectancy > 3 months For patients of reproductive potential (males and females), use of reliable means for contraception throughout the trial and for 6 months following their final exposure to study treatment Willingness and capability to be accessible for study follow-up Exclusion Criteria: Prior 5-FU, capecitabine, and/or oxaliplatin treatment with the exception of: prior oxaliplatin treatment≤ 6 weeks in the advanced or metastatic setting; prior treatment with 5-FU, capecitabine, and/or oxaliplatin in the adjuvant setting if relapse occurred > 6 months from concluding adjuvant therapy Peripheral neuropathy Grade ≥ 2 Prior radiotherapy to a measurable metastatic lesion(s) to be used for response assessment, unless the lesion has progressed subsequent to the radiotherapy Radiotherapy to a peripheral lesion within 14 days prior to Cycle 1, Day 1, or radiotherapy to a thoracic, abdominal, or pelvic field within 28 days prior to Cycle 1, Day 1 Chemotherapy, hormonal therapy, or immunotherapy within 4 weeks prior to Cycle 1, Day 1 Evidence of clinically detectable ascites Other invasive malignancies within 5 years prior to Cycle 1, Day 1 History or evidence upon physical examination of active central nervous system (CNS) disease Current or recent participation in another experimental drug study Clinically significant cardiovascular disease, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac arrhythmia within 1 year prior to Cycle 1, Day 1, or Grade II or greater peripheral vascular disease Active infection requiring parenteral antibiotics Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Cycle 1, Day 1, fine needle aspirations within 7 days prior to Cycle 1, Day 1, or anticipation of need for major surgical procedure during the course of the study Known or suspected to be positive for the human immunodeficiency virus (HIV) Known to be positive for hepatitis C or hepatitis B surface antigen Inadequately controlled hypertension Prior history of hypertensive crisis or hypertensive encephalopathy History of arterial thromboembolic event 6 months prior to Cycle 1, Day 1 History of abdominal fistula or gastrointestinal perforation within 6 months prior to Cycle 1, Day 1 Bleeding diathesis or coagulopathy Pregnancy (positive pregnancy test) or breast feeding Serious, non-healing wound, ulcer, or bone fracture

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: 1<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: FOLFOX<br>* Intravenous repeating dose<br>Drug: PRO95780<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose-limiting toxicities |  | Length and study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, nature, and severity of adverse events |  | Length of study | 
| Change in vital signs |  | Length of study | 
| Incidence and severity of infusion reactions |  | Length of study | 
| Change in clinical laboratory results |  | Length of study | 
| Incidence of anti-PRO95780 antibodies |  | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRC, Colon cancer, Avastin, APM4566g