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

Primary Purpose

Metastatic Colo-rectal Cancer

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
FOLFOXIRI + Panitumumab
Sponsored by
Gruppo Oncologico del Nord-Ovest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colo-rectal Cancer focused on measuring RAS Wild-Type, BRAF Wild-Type

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • P.O. Zona Aretina - Ospedale S. Donato Di Arezzo
  • Istituto Nazionale Per La Ricerca Sul Cancro
  • IRCCS Ospedale San Raffaele
  • Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio
  • Istituto Oncologico Veneto (IOV)
  • Polo Oncologico Area Vasta Nord-Ovest
  • Universita' Campus Bio-Medico Di Roma
  • Asl Di Sassari - Ospedale S.S. Annunziata -U.O. Oncologia Medica
  • Ausl 7 Di Siena
  • A.O. Universitaria S.Maria Della Misericordia Di Udine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFOXIRI + Panitumumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Response Rate
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
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
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
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
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
Exploratory analyses of potential predictive factors and surrogate markers of treatment activity or efficacy.

Full Information

First Posted
May 19, 2011
Last Updated
March 10, 2015
Sponsor
Gruppo Oncologico del Nord-Ovest
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1. Study Identification

Unique Protocol Identification Number
NCT01358812
Brief Title
FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer
Acronym
TRIP
Official Title
Phase II Trial of FOLFOXIRI Plus Panitumumab as First-Line Treatment for Kras and Braf Wild-Type Metastatic Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gruppo Oncologico del Nord-Ovest

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colo-rectal Cancer
Keywords
RAS Wild-Type, BRAF Wild-Type

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FOLFOXIRI + Panitumumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
FOLFOXIRI + Panitumumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response Rate
Description
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.
Time Frame
Up to 3 years (objective response will be evaluated every 8 weeks)
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
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.
Time Frame
Up to 3 years
Title
Overall Survival
Description
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.
Time Frame
Up to 3 years
Title
Safety Profile
Description
Safety Profile is based on the collection of all the adverse events occurring during the study graded by NCI-CTC criteria.
Time Frame
Up to 3 years
Title
Secondary Radical Surgery on Metastases
Description
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.
Time Frame
Up to 3 years
Title
Analyses of Potential Predictive Factors
Description
Exploratory analyses of potential predictive factors and surrogate markers of treatment activity or efficacy.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfredo Falcone, MD
Organizational Affiliation
Polo Oncologico Area Vasta Nord-Ovest
Official's Role
Principal Investigator
Facility Information:
Facility Name
P.O. Zona Aretina - Ospedale S. Donato Di Arezzo
City
Arezzo
Country
Italy
Facility Name
Istituto Nazionale Per La Ricerca Sul Cancro
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
IRCCS Ospedale San Raffaele
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio
City
Olbia
ZIP/Postal Code
07026
Country
Italy
Facility Name
Istituto Oncologico Veneto (IOV)
City
Padova
ZIP/Postal Code
35100
Country
Italy
Facility Name
Polo Oncologico Area Vasta Nord-Ovest
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Universita' Campus Bio-Medico Di Roma
City
Roma
ZIP/Postal Code
00128
Country
Italy
Facility Name
Asl Di Sassari - Ospedale S.S. Annunziata -U.O. Oncologia Medica
City
Sassari
ZIP/Postal Code
07100
Country
Italy
Facility Name
Ausl 7 Di Siena
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
A.O. Universitaria S.Maria Della Misericordia Di Udine
City
Udine
ZIP/Postal Code
33100
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
17470860
Citation
Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. doi: 10.1200/JCO.2006.09.0928.
Results Reference
background
PubMed Identifier
20921465
Citation
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.
Results Reference
background
PubMed Identifier
20921462
Citation
Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. doi: 10.1200/JCO.2009.27.6055. Epub 2010 Oct 4.
Results Reference
background
PubMed Identifier
20619739
Citation
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010 Aug;11(8):753-62. doi: 10.1016/S1470-2045(10)70130-3. Epub 2010 Jul 8.
Results Reference
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FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer

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