Maintenance Therapy With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction and Re-induction After Progress for 1st-line Treatment of Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This is a phase II, randomized, multi-center, open-label, parallel-group study to evaluate the progression-free survival during maintenance therapy. Eligible patients will be treated within a 12-week induction therapy. Those patients achieving CR/PR or SD at 12 weeks and qualifying for maintenance treatment and re-induction treatment with all potential drug components, will be randomized in a ratio of 1:1 to receive chemotherapy plus panitumumab or chemotherapy alone during maintenance. In case of progression, re-induction treatment will be started.

Official Title
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Randomized Phase II Study for Evaluation of Efficacy and Safety of Maintenance Treatment With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction Treatment With mFOLFOX6 Plus Panitumumab and Re-induction With mFOLFOX6 Plus Panitumumab in Case of Progression for First-line Treatment of Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Maintenance Chemotherapy
* Drug: Panitumumab (Within maintenance phase)
* Drug: mFOLFOX6 (Within re-induction phase)
* Drug: Panitumumab (Within re-induction phase)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Male or female ≥ 18 years of age Histologically proven metastatic colorectal cancer Molecular testing showing RAS wild-type in colorectal carcinoma cells Life expectancy > 12 weeks At least one measurable lesion according to RECIST 1.1 Adequate bone marrow, liver, kidney, organ and metabolic function Bone marrow function: leukocyte count ≥ 3.0 × 109/L ANC ≥ 1.5 × 109/L platelet count ≥ 100 × 109/L hemoglobin ≥ 9 g/dL or 5.59 mmol/L (may be transfused or treated with erythropoietin to maintain/ exceed this level) Hepatic function: Total bilirubin ≤ 1.5 × UNL ALT and AST ≤ 2.5 × UNL (or ≤ 5 × UNL in presence of liver metastases) AP ≤ 5 × UNL Renal function: Creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula or serum creatinine ≤ 1.5 × UNL Metabolic function: Magnesium ≥ lower limit of normal Calcium ≥ lower limit of normal ECOG performance status 0 - 1 Women of child-bearing potential must have a negative pregnancy test Exclusion Criteria: Previous treatment for colorectal cancer in the metastatic setting Previous EGFR-targeting therapy < 6 months after end of adjuvant therapy Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids Chronic inflammatory bowel disease Peripheral neuropathy ≥ NCI-CTCAE V 4.03 grade 2 Other previous malignancies with the exception of a history of previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up Significant disease that, in the investigator's opinion, would exclude the patient from the study History of cardiac disease; defined as: Congestive heart failure > New York Heart Association (NYHA) class 2 Active coronary artery disease (myocardial infarction more than 6 months prior to start of study treatment is allowed) Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted) Uncontrolled hypertension (defined as blood pressure ≥ 160 mmHg systolic and/or ≥ 90 mmHg diastolic on medication) Patients with interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan Known HIV, hepatitis B or C infection Known hypersensitivity reaction to any of the study components Radiotherapy, major surgery or any investigational drug 30 days before registration Pregnancy or lactation or planning to be pregnant during treatment and within 6 months after the end of treatment Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for at least an additional 6 months after the end of treatment Known alcohol or drug abuse Any condition that is unstable or could jeopardize the safety of the patient and his compliance in the study

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 |
| --- | --- |
| Experimental: Maintenance Chemotherapy + Panitumumab<br>Maintenance therapy: Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 | Drug: Maintenance Chemotherapy<br> <br> * Other names: Folinic acid + 5-FU (5-Fluorouracil);Drug: Panitumumab (Within maintenance phase)<br> <br> * Other names: Vectibix;Drug: mFOLFOX6 (Within re-induction phase)<br> <br> * Other names: Oxaliplatin + Folinic acid + 5-FU (5-Fluorouracil);Drug: Panitumumab (Within re-induction phase)<br> <br> * Other names: Vectibix;|
| Experimental: Maintenance Chemotherapy w/o Panitumumab<br>Maintenance therapy: Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 | Drug: Maintenance Chemotherapy<br> <br> * Other names: Folinic acid + 5-FU (5-Fluorouracil);Drug: mFOLFOX6 (Within re-induction phase)<br> <br> * Other names: Oxaliplatin + Folinic acid + 5-FU (5-Fluorouracil);Drug: Panitumumab (Within re-induction phase)<br> <br> * Other names: Vectibix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival during maintenance therapy defined as time from randomization until disease progression or death, whatever occurs first. | Until end of follow-up (24 months after randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| failure of treatment strategy | Time from randomization until failure (death/ progression) of treatment strategy | Until end of follow up (24 months after randomization) | 
| Progression-free survival of re-induction | Progression-free survival during re-induction therapy | From start of re-induction therapy until progress or end of follow-up (24 months after randomization) | 
| Objective response after 12 weeks of induction chemotherapy | Objective response after 12 weeks of induction chemotherapy | 12 weeks after start of induction chemotherapy | 
| Objective best response during maintenance and re-induction | Objective best response during maintenance and re-induction | Start of maintenance- until end of re-inductin therapy (expected average of 8 months) | 
| Overall survival | Overall survival measured from time of randomization and from time of registration | Until end of follow-up (24 months after randomization) | 
| Safety | Overall safety | Until end of follow-up (24 months after randomization) | 
| Health and skin related Quality of life | Health and skin related Quality of life | Until end of follow-up (24 months after randomization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic colorectal cancer, maintenance therapy, Panitumumab, Vectibix®