Randomized Phase II Study of First-Line FOLFOX Plus Panitumumab Versus 5FU Plus Panitumumab in RAS And BRAF Wild-Type Metastatic Colorectal Cancer Elderly Patients
Overview
- Phase
- Phase 2
- Intervention
- 5-fluorouracil
- Conditions
- Elderly Metastatic Colorectal Cancer Patients
- Sponsor
- Gruppo Oncologico del Nord-Ovest
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS). PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.
- Last Updated
- 5 years ago
Overview
Brief Summary
- Few data are available about the treatment of metastatic colorectal cancer (mCRC) elderly patients with anti-EGFR agents in combination with chemotherapy. Up today, most of the available data are from retrospective/post-hoc analyses, making them difficult to translate to everyday clinical practice.
- FOLFOX plus panitumumab is a standard first-line therapy option for RAS wild-type untreated mCRC patients. Slight adjustments in chemo-dosage are commonly applied in routinary practice to elderly patients, but those modified schedules have never been prospectively tested.
- In elderly patients, a reasonable upfront treatment is a fluoropyrimidine-based monotherapy plus bevacizumab, irrespectively of the molecular status of RAS.
- BRAF mutation is a strong negative prognostic factor associated to advanced age, poor performance status (PS), extended and aggressive disease and is associated to a lack of benefit from anti-EGFR moAb.
- Clinical definition of elderly (over 70 years old) CRC patients that may deserve a more or less intensive combination therapy is still debated. The cut-off of 75 years old combined with ECOG PS assessment is a reasonable approach for clearly defining candidates to different approaches31.
- Several geriatric screening tools have been used to identify patients with a geriatric profile potentially predicting for overall survival and risk of toxicity. The G8 screening tool has been validated in cancer patients showing the strongest prognostic value for overall survival; the CRASH score is able to stratify patients according an estimated risk of treatment-related toxicities.
On the basis of these considerations, the investigators designed the present randomized phase II trial of first-line therapy panitumumab in combination with simplified FOLFOX or with 5-fluorouracil, in previously untreated elderly patients with RAS and BRAF wild-type unresectable mCRC.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
FOLFOX plus panitumumab
* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * Oxaliplatin 85 mg/sqm iv over 2 hours, day 1; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Intervention: 5-fluorouracil
FOLFOX plus panitumumab
* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * Oxaliplatin 85 mg/sqm iv over 2 hours, day 1; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Intervention: oxaliplatin
FOLFOX plus panitumumab
* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * Oxaliplatin 85 mg/sqm iv over 2 hours, day 1; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Intervention: l-leucovorin
FOLFOX plus panitumumab
* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * Oxaliplatin 85 mg/sqm iv over 2 hours, day 1; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Intervention: panitumumab
5FU/LV plus panitumumab
* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Intervention: 5-fluorouracil
5FU/LV plus panitumumab
* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Intervention: l-leucovorin
5FU/LV plus panitumumab
* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Intervention: panitumumab
Outcomes
Primary Outcomes
Progression Free Survival (PFS). PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.
Time Frame: Up to 28 months
July 2016 - November 2018