A Study of Dulanermin Administered in Combination With the FOLFOX Regimen and Bevacizumab in Patients With Previously Untreated, Locally Advanced, Recurrent, or Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This is 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 Dulanermin Administered in Combination With the FOLFOX Regimen and Bevacizumab in Patients With Previously Untreated, Locally Advanced, Recurrent, or Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFOX regimen
* Drug: bevacizumab
* Drug: dulanermin


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 (i.e., by radiographic imaging or biopsy) 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 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 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 on Cycle 1, Day 1 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 or minor surgery (such as port placement) 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 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, or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: FOLFOX regimen<br>* Intravenous repeating dose<br>Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: dulanermin<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 |  | Until study discontinuation or the end of Cycle 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, nature, and severity of adverse events |  | Until study discontinuation or the end of Cycle 26 | 
| Change in vital signs |  | Until study discontinuation or the end of Cycle 26 | 
| Change in clinical laboratory results |  | Until study discontinuation or the end of Cycle 26 | 
| Incidence of anti-dulanermin antibodies |  | Until study discontinuation or the end of Cycle 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRC, Colon Cancer, Avastin, Apo2L/TRAIL