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 (VELO)

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colon Cancer
• Intervention / Treatment: Drug: Trifluridine Tipiracil; Drug: Panitumumab 20 MG/1 ML Intravenous Solution [VECTIBIX]

Detailed Description

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. The primary objective is to evaluate the efficacy [as defined by progression free survival (PFS)] of panitumumab in combination with Trifluridine-Tipiracil in pretreated mCRC patients. The secondary objective is to evaluate the objective response rate (ORR), overall survival (OS) and safety. Patients will be randomized in a 1:1 ratio to receive:

Arm A: Trifluridine-Tipiracil Arm B: Panitumumab + Trifluridine-Tipiracil A total of 112 patients will be enrolled. Treatment will be administered in 28-days cycles until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.

All patients will be closely monitored for safety and tolerability during all cycles of therapy, at the treatment discontinuation visit, and during the follow-up period. The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (v. 5.0) will be used to characterize the toxicity profile of the study treatments on all patients. Patients who discontinue treatment for reasons other than disease progression (e.g., toxicity) will continue scheduled tumor assessments until disease progression, withdrawal of consent, study termination by Sponsor, or death, whichever occurs first. In the absence of disease progression, tumor assessments should continue regardless of whether patients start a new anti-cancer therapy, unless consent is withdrawn. All patients will be followed for survival unless consent is withdrawn.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Catania, Italy
    • A.R.N.A.S. Garibaldi - P.O. GaribaldiNesima
  • Milano, Italy
    • Istituto Europeo Di Oncologia
  • Napoli, Italy, 80131
    • AORN-Ospedale dei colli, UOC Oncologia
  • Napoli, Italy
    • A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"
  • Napoli, Italy
    • IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale"
  • Roma, Italy
    • Universiyà Campus-Biomedico
  • CA
    • Monserrato, CA, Italy
      • A.O.U. Cagliari - Presidio Policlinico D. Casula
  • PI
    • Pisa, PI, Italy
      • A.O.U. Pisana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Trifluridine-Tipiracil	Drug: Trifluridine Tipiracil; 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
Experimental: Arm B; Panitumumab + Trifluridine-Tipiracil	Drug: Trifluridine Tipiracil; 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; Drug: Panitumumab 20 MG/1 ML Intravenous Solution [VECTIBIX]; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	ORR: per the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1), defined as the number of patients achieving an overall best response of complete or partial response divided by the total number of patients	from screening up to 30 months
OS	OS: defined as the time from randomization to death due to any cause of panitumumab in combination with Trifluridine-Tipiracil vs Trifluridine-Tipiracil	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).	To explore the safety and tolerability of panitumumab in combination with Trifluridine-Tipiracil vs standard third line therapy (Trifluridine-Tipiracil)	from screening up to 30 months

Collaborators and Investigators

• Sponsor: University of Campania "Luigi Vanvitelli"
• Investigators: Principal Investigator: Fortunato Ciardiello, A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2019
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: July 19, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Panitumumab; Trifluridine
• Other Study ID Numbers: VELO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No