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
Overview
- Phase
- Phase 2
- Intervention
- Maintenance Chemotherapy
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- AIO-Studien-gGmbH
- Enrollment
- 387
- Locations
- 2
- Primary Endpoint
- Progression-free survival
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
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)
Arms & Interventions
Maintenance Chemotherapy + Panitumumab
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
Intervention: Maintenance Chemotherapy
Maintenance Chemotherapy + Panitumumab
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
Intervention: Panitumumab (Within maintenance phase)
Maintenance Chemotherapy + Panitumumab
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
Intervention: mFOLFOX6 (Within re-induction phase)
Maintenance Chemotherapy + Panitumumab
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
Intervention: Panitumumab (Within re-induction phase)
Maintenance Chemotherapy w/o Panitumumab
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
Intervention: Maintenance Chemotherapy
Maintenance Chemotherapy w/o Panitumumab
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
Intervention: mFOLFOX6 (Within re-induction phase)
Maintenance Chemotherapy w/o Panitumumab
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
Intervention: Panitumumab (Within re-induction phase)
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: Until end of follow-up (24 months after randomization)
Progression-free survival during maintenance therapy defined as time from randomization until disease progression or death, whatever occurs first.
Secondary Outcomes
- failure of treatment strategy(Until end of follow up (24 months after randomization))
- Progression-free survival of re-induction(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(12 weeks after start of induction chemotherapy)
- Objective best response during maintenance and re-induction(Start of maintenance- until end of re-inductin therapy (expected average of 8 months))
- Overall survival(Until end of follow-up (24 months after randomization))
- Safety(Until end of follow-up (24 months after randomization))
- Health and skin related Quality of life(Until end of follow-up (24 months after randomization))