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

NCT05468892 | Completed Phase 2

• 1 other identifier: VELO
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Metastatic Colon Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  PFS: defined as the time from randomization to the earliest documented disease progression or death due to any cause of panitumumab in combination with Trifluridine-Tipiracil vs Trifluridine-Tipiracil"

  from screening up to 30 months

Secondary Outcomes (3)

• ORR

  from screening up to 30 months

• OS

  from screening up to 30 months

• Safety and tolerability analysis: defined as the evaluation of incidence and severity of AEs, graded according to NCI- CTCAE, version 5.0 (v. 5.0).

  from screening up to 30 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Trifluridine-Tipiracil

Drug: Trifluridine Tipiracil

Arm B

EXPERIMENTAL

Panitumumab + Trifluridine-Tipiracil

Drug: Trifluridine Tipiracil; Drug: Panitumumab 20 MG/1 ML Intravenous Solution [VECTIBIX]

Interventions

Trifluridine Tipiracil DRUG

Trifluridine-Tipiracil will be administered at 35 mg per square meter orally twice daily, with a glass of water within 1 hour after completion of morning and evening meals, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest period. One treatment cycle with Trifluridine-Tipiracil consists of the following: Days 1-5: Trifluridine / Tipiracil (35 mg/m2/dose) orally twice daily Days 6-7: Rest Days 8-12: Trifluridine / Tipiracil(35mg/m²/dose) orally twice daily Days 13-28: Rest

Arm A; Arm B

Panitumumab 20 MG/1 ML Intravenous Solution [VECTIBIX] DRUG

Panitumumab will be administered as a 6 mg/kg intravenous infusion over 60 minutes every 2 weeks (q2w) of a 28-day cycle (Day 1 and Day 15).

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (8)

A.O.U. Cagliari - Presidio Policlinico D. Casula

Monserrato, CA, Italy

Location

A.O.U. Pisana

Pisa, PI, Italy

Location

A.R.N.A.S. Garibaldi - P.O. GaribaldiNesima

Catania, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

AORN-Ospedale dei colli, UOC Oncologia

Napoli, 80131, Italy

Location

A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"

Napoli, Italy

Location

IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale"

Napoli, Italy

Location

Universiyà Campus-Biomedico

Roma, Italy

Location

Related Publications (3)

• Ciardiello 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 DERIVED

• Napolitano 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 DERIVED

• Napolitano 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 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

trifluridine tipiracil drug combination; Panitumumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Fortunato Ciardiello

  A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: July 21, 2022
• Study Start: October 29, 2019
• Primary Completion: May 31, 2022
• Study Completion: June 30, 2022
• Last Updated: February 1, 2024

Record last verified: 2024-01

Locations

IT (8)