A Study of PRO95780 in Combination With Cetuximab and Irinotecan Chemotherapy or the FOLFIRI Regimen With Bevacizumab in Patients With Previously Treated Metastatic Colorectal Cancer (APM4187g)

Study Overview
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Brief Summary
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This is a Phase Ib, open-label, multicenter, dose-escalation study designed to assess if PRO95780 in combination with two different irinotecan-containing regimens is safe and tolerable in patients with metastatic colorectal cancer (mCRC) who have progressed following, or cannot tolerate, first-line therapy with 5-fluorouracil-, oxaliplatin-, and bevacizumab-containing regimens. This study will also make a preliminary assessment of the anti-tumor activity of PRO95780 in combination with irinotecan and cetuximab or the FOLFIRI regimen plus bevacizumab.

Official Title
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A Phase Ib, Dose-Escalation Study of the Safety and Pharmacokinetics of PRO95780 in Combination With Cetuximab and Irinotecan Chemotherapy or the FOLFIRI Regimen With Bevacizumab in Patients With Previously Treated Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab
* Drug: cetuximab
* Drug: FOLFIRI regimen
* Drug: irinotecan
* Drug: PRO95780


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age ≥ 18 years Histologically confirmed CRC with evidence of metastases and measurable tumor lesions Documented disease progression following, or intolerance to, treatment with 5-fluorouracil, oxaliplatin, and bevacizumab-based therapy Life expectancy > 3 months For patients of reproductive potential (males and females), use of reliable means for contraception (e.g., contraceptive pill, intrauterine device [IUD], physical barrier) 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: Patients who have a Kras mutation will be excluded from receiving cetuximab-containing regimens Prior radiotherapy to a measurable metastatic lesion(s) to be used for response assessment, unless the lesion has progressed subsequent to the radiotherapy Recent radiotherapy to a peripheral lesion, thoracic, abdominal, or pelvic field Recent chemotherapy, hormonal therapy, or immunotherapy Evidence of clinically detectable ascites Other invasive malignancies within 5 years History or evidence of active central nervous system (CNS) disease Current or recent participation in another experimental drug study Clinically significant cardiovascular disease Active infection requiring parenteral antibiotics Recent major surgical procedure, open biopsy, significant traumatic injury, fine needle aspirations, 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 History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or specified study treatment Pregnancy (positive pregnancy test) or breast feeding Serious, non-healing wound, ulcer, or bone fracture Known sensitivity to any of the products administered during the study Any disorder that compromises the ability of the patient to provide written informed consent and/or comply with study procedures

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: cetuximab<br>* Intravenous repeating dose<br>Drug: irinotecan<br>* Intravenous repeating dose<br>Drug: PRO95780<br>* Intravenous repeating dose<br>|
| Experimental: 2<br> | Drug: bevacizumab<br>* (Only for patients not previously treated with bevacizumab) Intravenous repeating dose<br>Drug: FOLFIRI regimen<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 |  | Through study completion or early study discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, nature, and severity of adverse events |  | Through study completion or early study discontinuation | 
| Change in vital signs |  | Through study completion or early study discontinuation | 
| Incidence and severity of infusion reactions |  | Through study completion or early study discontinuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRC, Colon cancer, Avastin, APM4187g