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)

• ClinicalTrials.gov Identifier: NCT05468892
• Recruitment Status: Completed
• First Posted: July 21, 2022
• Last Update Posted: February 1, 2024
• Sponsor: University of Campania "Luigi Vanvitelli"
• Information provided by (Responsible Party): Fortunato Ciardiello, University of Campania "Luigi Vanvitelli"

Tracking Information

• First Submitted Date: July 19, 2022
• First Posted Date: July 21, 2022
• Last Update Posted Date: February 1, 2024
• Actual Study Start Date: October 29, 2019
• Actual Primary Completion Date: May 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 19, 2022)

PFS [ Time Frame: 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"

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 21, 2022)

• ORR [ Time Frame: 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 [ Time Frame: 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). [ Time Frame: 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)

Original Secondary Outcome Measures (submitted: July 19, 2022)

• ORR [ Time Frame: 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 [ Time Frame: 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 analysis [ Time Frame: from screening up to 30 months ]
  Safety analysis: defined as the evaluation of incidence and severity of Adverse Events (AEs), graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (v. 5.0) of panitumumab in combination with Trifluridine-Tipiracil vs standard third line therapy (Trifluridine-Tipiracil)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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
• 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colon Cancer

Intervention

• 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).

Study Arms

• Active Comparator: Arm A
  Trifluridine-Tipiracil
  Intervention: Drug: Trifluridine Tipiracil
• Experimental: Arm B
  Panitumumab + Trifluridine-Tipiracil
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 19, 2022): 68
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: June 30, 2022
• Actual Primary Completion Date: May 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT05468892
• Other Study ID Numbers: VELO
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fortunato Ciardiello, University of Campania "Luigi Vanvitelli"
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Campania "Luigi Vanvitelli"
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Campania "Luigi Vanvitelli"
• Verification Date: January 2024