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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gruppo Oncologico del Nord-Ovest
ClinicalTrials.gov Identifier:
NCT01358812
First received: May 19, 2011
Last updated: March 10, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Metastatic Colo-rectal Cancer
Drug: FOLFOXIRI + Panitumumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of FOLFOXIRI Plus Panitumumab as First-Line Treatment for Kras and Braf Wild-Type Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Gruppo Oncologico del Nord-Ovest:

Primary Outcome Measures:
  • Response Rate [ Time Frame: Up to 3 years (objective response will be evaluated every 8 weeks) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Safety Profile [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Safety Profile is based on the collection of all the adverse events occurring during the study graded by NCI-CTC criteria.

  • Secondary Radical Surgery on Metastases [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Analyses of Potential Predictive Factors [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Exploratory analyses of potential predictive factors and surrogate markers of treatment activity or efficacy.


Enrollment: 37
Study Start Date: March 2010
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01358812

Locations
Italy
P.O. Zona Aretina - Ospedale S. Donato Di Arezzo
Arezzo, Italy
Istituto Nazionale Per La Ricerca Sul Cancro
Genova, Italy, 16132
IRCCS Ospedale San Raffaele
Milano, Italy, 20132
Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio
Olbia, Italy, 07026
Istituto Oncologico Veneto (IOV)
Padova, Italy, 35100
Polo Oncologico Area Vasta Nord-Ovest
Pisa, Italy, 56126
Universita' Campus Bio-Medico Di Roma
Roma, Italy, 00128
Asl Di Sassari - Ospedale S.S. Annunziata -U.O. Oncologia Medica
Sassari, Italy, 07100
Ausl 7 Di Siena
Siena, Italy, 53100
A.O. Universitaria S.Maria Della Misericordia Di Udine
Udine, Italy, 33100
Sponsors and Collaborators
Gruppo Oncologico del Nord-Ovest
Investigators
Principal Investigator: Alfredo Falcone, MD Polo Oncologico Area Vasta Nord-Ovest
  More Information

Publications:

Responsible Party: Gruppo Oncologico del Nord-Ovest
ClinicalTrials.gov Identifier: NCT01358812     History of Changes
Other Study ID Numbers: 2934, 2009-014556-29
Study First Received: May 19, 2011
Last Updated: March 10, 2015
Health Authority: Italy: Italian Agency for Drugs (AIFA)

Keywords provided by Gruppo Oncologico del Nord-Ovest:
RAS Wild-Type
BRAF Wild-Type

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 03, 2015