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

Sponsor

University of Campania "Luigi Vanvitelli" (Other)

Overall Status

Completed

CT.gov ID

NCT05468892

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

8.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colon Cancer	Drug: Trifluridine Tipiracil Drug: Panitumumab 20 MG/1 ML Intravenous Solution [VECTIBIX]	Phase 2

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tumor assessments should continue regardless of whether patients start a new anti-cancer therapy, unless consent is withdrawn. All patients will be followed for survival unless consent is withdrawn.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 Design

Study Type:

Interventional

Actual Enrollment :

68 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 29, 2019

Actual Primary Completion Date :

May 31, 2022

Actual Study Completion Date :

Jun 30, 2022

Arms and Interventions

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).

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

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).

Outcome Measures

Primary Outcome Measures

PFS [from screening up to 30 months]
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"

Secondary Outcome Measures

ORR [from screening up to 30 months]
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
OS [from screening up to 30 months]
OS: defined as the time from randomization to death due to any cause of panitumumab in combination with Trifluridine-Tipiracil vs Trifluridine-Tipiracil
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]
To explore the safety and tolerability of panitumumab in combination with Trifluridine-Tipiracil vs standard third line therapy (Trifluridine-Tipiracil)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A.O.U. Cagliari - Presidio Policlinico D. Casula	Monserrato	CA	Italy
2	A.O.U. Pisana	Pisa	PI	Italy
3	A.R.N.A.S. Garibaldi - P.O. GaribaldiNesima	Catania		Italy
4	Istituto Europeo di Oncologia	Milano		Italy
5	AORN-Ospedale dei colli, UOC Oncologia	Napoli		Italy	80131
6	A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"	Napoli		Italy
7	IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale"	Napoli		Italy
8	Universiyà Campus-Biomedico	Roma		Italy

Sponsors and Collaborators

University of Campania "Luigi Vanvitelli"

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Fortunato Ciardiello, Principle Investigator, University of Campania "Luigi Vanvitelli"

ClinicalTrials.gov Identifier:

NCT05468892

Other Study ID Numbers:

VELO

First Posted:

Jul 21, 2022

Last Update Posted:

Jul 26, 2022

Last Verified:

Jul 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Colorectal Neoplasms

Trifluridine

Panitumumab

Study Results

No Results Posted as of Jul 26, 2022