FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer (TRIP)

March 10, 2015 updated by: Gruppo Oncologico del Nord-Ovest

Phase II Trial of FOLFOXIRI Plus Panitumumab as First-Line Treatment for Kras and Braf Wild-Type Metastatic Colorectal Cancer

The GONO-FOLFOXIRI regimen demonstrated higher activity and efficacy compared to FOLFIRI in a phase III trial. Panitumumab with oxaliplatin- or irinotecan-based doublets is feasible and associated with improved activity in KRAS codon 12-13 wild-type patients. BRAF and other RAS rare mutations have been suggested as additional potential biomarkers for anti-EGFR agents in metastatic colo-rectal cancer. The present study aims to demonstrate the feasibility and the activity of the first-line combination of the GONO-FOLFOXIRI regimen and Panitumumab in molecularly selected metastatic colo-rectal cancer patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Arezzo, Italy
        • P.O. Zona Aretina - Ospedale S. Donato Di Arezzo
      • Genova, Italy, 16132
        • Istituto nazionale Per la Ricerca sul Cancro
      • Milano, Italy, 20132
        • IRCCS Ospedale San Raffaele
      • Olbia, Italy, 07026
        • Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio
      • Padova, Italy, 35100
        • Istituto Oncologico Veneto (IOV)
      • Pisa, Italy, 56126
        • Polo Oncologico Area Vasta Nord-Ovest
      • Roma, Italy, 00128
        • Universita' Campus Bio-Medico Di Roma
      • Sassari, Italy, 07100
        • Asl Di Sassari - Ospedale S.S. Annunziata -U.O. Oncologia Medica
      • Siena, Italy, 53100
        • Ausl 7 Di Siena
      • Udine, Italy, 33100
        • A.O. Universitaria S.Maria Della Misericordia Di Udine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed colorectal adenocarcinoma;
  • Availability of formalin-fixed paraffin embedded tumor block from primary or metastasis;
  • KRAS and BRAF wild-type status of primary colorectal cancer or related metastasis;
  • Unresectable and measurable metastatic disease according to RECIST criteria;
  • Male or female, aged >/= 18 years and </= 75 years;
  • ECOG PS < 2 if aged < 71 years;
  • ECOG PS = 0 if aged 71-75 years;
  • Life expectancy of more than 3 months;
  • Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL;
  • Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN);
  • Serum creatinine ≤ 1.5 x ULN;
  • Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
  • At least 6 weeks from prior radiotherapy and 4 weeks from surgery;
  • Written informed consent to experimental treatment and pharmacogenomic analyses;
  • Magnesium ≥ lower limit of normal;
  • Calcium ≥ lower limit of normal.

Exclusion Criteria:

  • Prior palliative chemotherapy;
  • Prior treatment with EGFR inhibitors;
  • Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria;
  • Presence or history of CNS metastasis;
  • Active uncontrolled infections; active disseminated intravascular coagulation;
  • Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix;
  • Clinically significant cardiovascular disease, for example cerebrovascular accidents (CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia;
  • Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception;
  • Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment;
  • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: FOLFOXIRI + Panitumumab
PANITUMUMAB 6 mg/Kg i.v. over 1 hour followed by IRINOTECAN 150 mg/sqm i.v. over 1 hour followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hours concomitantly with L-LV 200 mg/sqm over 2 hours followed by 5-FLUOROURACIL 2400 mg/sqm c.i. over 48 hours starting on day 1 repeated every 2 weeks.
Drug: FOLFOXIRI + Panitumumab
PANITUMUMAB 6 mg/Kg i.v. over 1 hour followed by IRINOTECAN 150 mg/sqm i.v. over 1 hour followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hours concomitantly with L-LV 200 mg/sqm over 2 hours followed by 5-FLUOROURACIL* 2400 mg/sqm c.i. over 48 hours starting on day 1 repeated every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: Up to 3 years (objective response will be evaluated every 8 weeks)
Response rate is defined as the fraction of treated patients who achieve a response as defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria vers. 1.1.
Up to 3 years (objective response will be evaluated every 8 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: Up to 3 years
Progression free survival is defined as time from study entry until progression of disease (according to RECIST 1.1) or death from any cause. Patients who are alive without having progressed at the end of the study will be censored at their last radiological assessment.
Up to 3 years
Overall Survival
Time Frame: Up to 3 years
Overall survival is defined as the time from study entry until death from any cause. Patients who are alive at the end of the study will be censored at that point.
Up to 3 years
Safety Profile
Time Frame: Up to 3 years
Safety Profile is based on the collection of all the adverse events occurring during the study graded by NCI-CTC criteria.
Up to 3 years
Secondary Radical Surgery on Metastases
Time Frame: Up to 3 years
Secondary Radical Surgery on Metastases is defined as microscopically margin-free complete surgical removal of all residual disease performed during treatment or after its completion allowed by tumoral shrinkage and or desappearance of one or more lesions.
Up to 3 years
Analyses of Potential Predictive Factors
Time Frame: Up to 3 years
Exploratory analyses of potential predictive factors and surrogate markers of treatment activity or efficacy.
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Oncologico del Nord-Ovest

Investigators

  • Principal Investigator: Alfredo Falcone, MD, Polo Oncologico Area Vasta Nord-Ovest

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (ACTUAL)

October 1, 2011

Study Registration Dates

First Submitted

May 19, 2011

First Submitted That Met QC Criteria

May 23, 2011

First Posted (ESTIMATE)

May 24, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

March 11, 2015

Last Update Submitted That Met QC Criteria

March 10, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2934
  • 2009-014556-29 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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