Panitumumab-based Maintenance in Patients With RAS Wild-type, Metastatic Colorectal Cancer (Valentino)
Summary
Open label, randomized, multicenter, phase II study to compare the efficacy, in terms of non-inferiority of progression-free survival (PFS), of maintenance with panitumumab alone (arm B) as compared to panitumumab with 5-fluorouracil (5-FU) and leucovorin (LV) (arm A) following induction treatment with 5-fluorouracil + leucovorin+oxaliplatin (FOLFOX-4) and panitumumab in patients with RAS wild-type, metastatic colorectal cancer. The study involves an induction phase with panitumumab as 1 hour intravenous infusion at the dosage of 6 mg/kg, given every two weeks, plus FOLFOX-4 chemotherapy as standard guidelines. Before start of FOLFOX-4 plus panitumumab, at the time of enrollment, patients will be immediately randomized electronically 1:1 to one of the two maintenance arms. Induction treatment with FOLFOX-4 plus panitumumab will continue until progressive disease, unacceptable toxicity or informed consent withdrawal, or for up to 8 cycles. At the end of induction treatment, in presence of complete or partial response, or stable disease, non-progressing patients will be allocated to one of the two pre-assigned maintenance arms: A) 5-FU/LV (De Gramont regimen) plus panitumumab given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal B) Panitumumab alone given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal Imaging studies (thorax and abdominal CT or MRI scan) will be performed at baseline (4 weeks prior enrollment) and every 8 weeks (4 cycles) during treatment.
Timeline
- Start
- 2015-06
- Primary completion
- 2018-07
- Completion
- 2018-07
Outcome
Missed primary endpoint
paper Arm B was inferior (upper limit of 1-sided 90% CI of the HR, 1.857). PMID 31268481 ↗
paper maintenance therapy with single-agent panitumumab was inferior in terms of PFS compared with panitumumab plus fluorouracil-leucovorin PMID 31268481 ↗
Publications
- Morano F, Corallo S, Lonardi S, Raimondi A, Cremolini C, Rimassa L, Murialdo R, Zaniboni A, Sartore-Bianchi A, Tomasello G, Racca P, Clavarezza M, Adamo V, Perrone F, Gloghini A, Tamborini E, Busico A, Martinetti A, Palermo F, Loupakis F, Milione M, Fuca G, Di Bartolomeo M, de Braud F, Pietrantonio F. Negative Hyperselection of Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer Who Received Panitumumab-Based Maintenance Therapy. J Clin Oncol. 2019 Nov 20;37(33):3099-3110. doi: 10.1200/JCO.19.01254. Epub 2019 Sep 20.
- Pietrantonio F, Morano F, Corallo S, Miceli R, Lonardi S, Raimondi A, Cremolini C, Rimassa L, Bergamo F, Sartore-Bianchi A, Tampellini M, Racca P, Clavarezza M, Berenato R, Caporale M, Antista M, Niger M, Smiroldo V, Murialdo R, Zaniboni A, Adamo V, Tomasello G, Giordano M, Petrelli F, Longarini R, Cinieri S, Falcone A, Zagonel V, Di Bartolomeo M, de Braud F. Maintenance Therapy With Panitumumab Alone vs Panitumumab Plus Fluorouracil-Leucovorin in Patients With RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1268-1275. doi: 10.1001/jamaoncol.2019.1467.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Leucovorin | Small molecule | 200 mg/m2 | — |
| Subject | Panitumumab | Monoclonal antibody | 6 mg/kg | Intravenous |
| Comparator | fluorouracil | Small molecule | 400 mg/m2 | — |
| Comparator | fluorouracil | Small molecule | 600 mg/m2 | — |
| Background | Oxaliplatin | Small molecule | 85 mg/m2 | — |