Phase II Randomized Study Evaluating the Efficacy of Panitumumab (VEctibix ) and Trifluridine-Tipiracil (LOnsurf) in Pretreated RAS Wild Type Metastatic Colorectal Cancer Patients: the VELO Trial

This is a randomized phase II, open label, two arm study, evaluating the efficacy of panitumumab in combination with Trifluridine-Tipiracilas third line therapy, after a first line containing an anti-EGFR agent panitumumab(at least 70% of study population) or cetuximab in metastatic colorectal cancer (mCRC) patients.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Histologically proven diagnosis of colorectal adenocarcinoma
* Diagnosis of metastatic disease
* RAS (NRAS and KRAS exon 2,3 and 4) wild-type in tissue at initial diagnosis
* Efficacy of a first line therapy containing an anti-EGFR agent (panitumumab or ceuximab) with a major response achieved (complete or partial response)
* Progression after a second line therapy
* Available and adequate baseline tumour tissue sample
* Measurable disease according to RECIST criteria v1.1
* Male or female patients \> 18 years of age
* ECOG Performance Status 0-1
* Life expectancy of at least 3 months
* Adequate bone marrow, liver and renal function
* If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 14 days before initiation of study treatment
* If female and of childbearing potential, or if male, agreement to use adequate contraception (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method)
* Signed informed consent

Exclusion Criteria:

* Any contraindication to use Trifluridine - Tipiracil or Panitumumab
* More than two previous lines of treatment
* Active uncontrolled infections
* Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
* Pregnancy
* Breastfeeding
* Interstitial lung disease or pulmonary fibrosis
* Grade III or IV heart failure (NYHA classification)

• DERIVEDCiardiello D, Martinelli E, Troiani T, Mauri G, Rossini D, Martini G, Napolitano S, Famiglietti V, Del Tufo S, Masi G, Santini D, Avallone A, Pietrantonio F, Lonardi S, Di Maio M, Zampino MG, Fazio N, Bardelli A, Siena S, Cremolini C, Sartore-Bianchi A, Ciardiello F. Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer: A Nonrandomized Controlled Trial. JAMA Netw Open. 2024 Apr 1;7(4):e245635. doi: 10.1001/jamanetworkopen.2024.5635. PMID 38592721
• DERIVEDNapolitano S, Ciardiello D, De Falco V, Martini G, Martinelli E, Della Corte CM, Esposito L, Famiglietti V, Di Liello A, Avallone A, Cardone C, De Stefano A, Montesarchio V, Zampino MG, Fazio N, Di Maio M, Del Tufo S, De Vita F, Altucci L, Marrone F, Ciardiello F, Troiani T. Panitumumab plus trifluridine/tipiracil as anti-EGFR rechallenge therapy in patients with refractory RAS wild-type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase II VELO trial. Int J Cancer. 2023 Oct 15;153(8):1520-1528. doi: 10.1002/ijc.34632. Epub 2023 Jun 30. PMID 37391938
• DERIVEDNapolitano S, De Falco V, Martini G, Ciardiello D, Martinelli E, Della Corte CM, Esposito L, Famiglietti V, Di Liello A, Avallone A, Cardone C, De Stefano A, Montesarchio V, Zampino MG, Bordonaro R, Scartozzi M, Santini D, Di Maio M, De Vita F, Altucci L, Marrone F, Ciardiello F, Troiani T. Panitumumab Plus Trifluridine-Tipiracil as Anti-Epidermal Growth Factor Receptor Rechallenge Therapy for Refractory RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2023 Jul 1;9(7):966-970. doi: 10.1001/jamaoncol.2023.0655. PMID 37200022