PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study

Study Overview
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Brief Summary
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The purpose of this study is to assess whether treatment with the study drug, panitumumab given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive concomitant panitumumab therapy.

Official Title
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PACCE: A Randomized, Open-Label, Controlled, Clinical Trial of Chemotherapy and Bevacizumab With and Without Panitumumab in the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Oxaliplatin Based Chemotherapy
* Drug: Panitumumab
* Drug: Irinotecan Based Chemotherapy
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adenocarcinoma of the colon or rectum Metastatic colorectal cancer (mCRC) Measurable disease per modified response evaluation criteria in solid tumors (RECIST) criteria ECOG performance status of 0 or 1 Available paraffin-embedded tumor tissue (from primary tumor or metastasis) or unstained slides of paraffin-embedded tissue If history of other primary cancer, subject will be eligible only if she or he has: Curatively resected non-melanomatous skin cancer; Curatively treated cervical carcinoma in situ; Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 5 years. Adequate hematologic data as follows: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9 cells/L; Platelet count greater than or equal to 100 x 10^9/L; Hemoglobin greater than or equal to 9.0 g/dL. - Adequate renal function: Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN); Urinary protein dipstick of less than 2+ (if urinary dipstick 2+ or greater, then excretion of less than or equal to 1000 mg of protein per day as determined by 24-hour urine collection). Adequate hepatic function: Alkaline phosphatase less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN); Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)(AST) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN); Alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN); Bilirubin less than or equal to 2 x ULN. - Competent to comprehend, sign, and date an IRB-approved informed consent form Before any study-specific procedure, the appropriate written informed consent must be obtained. Exclusion Criteria: Prior chemotherapy or biologic (i.e., antibody or vaccine) treatment for mCRC disease - Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before randomization - Radiotherapy within 14 days before randomization Elective and/or planned major surgical procedure to be performed during the course of this trial (surgery that arises as needed or necessary during the course of the study, not agreed a priori, will not make the subject ineligible) Major surgery within 28 days before randomization Central nervous system metastases History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan Clinically significant ascites Preexisting bleeding diathesis or coagulopathy or the need for full-dose anticoagulation Any of the following within 1 year before randomization: Myocardial infarction; Unstable angina; Symptomatic congestive heart failure; Serious uncontrolled cardiac arrhythmia; Cerebrovascular accident or transient ischemic attack; Gastrointestinal ulcer or hemorrhage; Hemoptysis; Pulmonary embolism; Deep vein thrombosis, or other significant thromboembolic event. Regular use of non-steroidal anti-inflammatory agents Female subject of childbearing potential, not abstinent, and not willing to use contraceptives during the course of the study and for 6 months following the last dose of first-line treatment Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization Male subject, not abstinent, and not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of first-line treatment Subject known to be human immunodeficiency virus (HIV) positive Subject allergic to panitumumab or any components of panitumumab formulation History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results Subject unwilling or unable to comply with study requirements Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxaliplatin and bevacizumab without panitumumab<br>Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone. | Drug: Oxaliplatin Based Chemotherapy<br>* Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.<br>* Other names: Oxaliplatin;Drug: Bevacizumab<br>* Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .<br>* Other names: Avastin;|
| Experimental: Irinotecan and bevacizumab plus panitumumab<br>Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W | Drug: Panitumumab<br>* PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.<br>* Other names: Vectibix;Drug: Irinotecan Based Chemotherapy<br>* Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.<br>* Other names: Douillard;Drug: Bevacizumab<br>* Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .<br>* Other names: Avastin;|
| Active Comparator: Irinotecan and bevacizumab without panitumumab<br>Irinotecan-based chemotherapy and Bevacizumab Q2W alone | Drug: Irinotecan Based Chemotherapy<br>* Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.<br>* Other names: Douillard;Drug: Bevacizumab<br>* Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .<br>* Other names: Avastin;|
| Experimental: Oxaliplatin and bevacizumab plus panitumumab<br>Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W | Drug: Oxaliplatin Based Chemotherapy<br>* Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.<br>* Other names: Oxaliplatin;Drug: Panitumumab<br>* PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.<br>* Other names: Vectibix;Drug: Bevacizumab<br>* Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (Oxaliplatin) | Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression | Overall study | 
| Objective Tumor Response Through Week 12 (Irinotecan) | Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum | Overall Study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (Oxaliplatin) | Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin | Overall study | 
| Objective Tumor Response Rate (Oxaliplatin) | Best overall response of complete or partial response within oxaliplatin stratum | Overall study | 
| Time to Progression (Oxaliplatin) | Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the oxaliplatin stratum | Overall Study | 
| Time to Treatment Failure (Oxaliplatin) | Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the oxaliplatin stratum. | Overall study | 
| Overall Survival (Irinotecan) | Incidence of mortality from any cause in groups treated with Irinotecan. Incidence is provided in lieu of the median time to death since the median or its measure of dispersion was not estimable for at least one treatment arm. | Overall study | 
| Progression-free Survival (Irinotecan) | Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression | Overall Study | 
| Objective Tumor Response Rate (Irinotecan) | Best overall response of complete or partial response within irinotecan stratum | Overall Study | 
| Time to Progression (Irinotecan) | Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the irinotecan stratum | Overall Study | 
| Time to Treatment Failure (Irinotecan) | Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the irinotecan stratum | Overall Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Panitumumab Advanced Colorectal Cancer Evaluation Study (PACCE Study), Colorectal, Colon, Rectal Cancer, Metastatic Colorectal, EGFr, Clinical Trial, Panitumumab, ABX-EGF, Immunex, Abgenix, Amgen, Metastatic Colorectal Cancer, Oncology