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

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tumor assessments should continue regardless of whether patients start a new anti-cancer therapy, unless consent is withdrawn. All patients will be followed for survival unless consent is withdrawn.

Official Title
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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

Conditions
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Metastatic Colon Cancer

Intervention / Treatment
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* Drug: Trifluridine Tipiracil
* Drug: Panitumumab 20 MG/1 ML Intravenous Solution [VECTIBIX]


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |