A Clinical Trial of Panitumumab in Combination With FOLFIRI Chemotherapy as Second Line Treatment in Subjects With Metastatic Colorectal Cancer Expressing Wild-type KRAS and Who Had Progressed ≥ 6 Months After the Last Dose of the First Line Chemotherapy (ACTIVE)
First line chemotherapy treatment regimens for metastatic colorectal cancer (mCRC) present disease-free survival of more than 10 months, and as much as 12 and 15 months for many patients.
It is evident that there are 2 groups of patients with metastatic colorectal cancer(mCRC): those who progress during first line treatment or in the 6 months following the last chemotherapy infusion and those who progress after this first 6-month period.
There are currently no studies evaluating the efficacy of second line chemotherapy regimens according to the duration of response to first line treatment. It seems logical that patients with less aggressive tumours will benefit more from treatments targeting specific proteins, such as panitumumab, due to the shorter duration of these tumours cell cycle, which makes them less sensitive to chemotherapy.
This study is therefore justified to determine an increase in activity and control of the disease in patients who progressed after 6 months of the last first line chemotherapy infusion for metastatic colorectal cancer(mCRC) in subjects expressing wild-type KRAS.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Phase II Clinical Trial of Panitumumab in Combination With FOLFIRI Chemotherapy as Second Line Treatment in Subjects With Metastatic Colorectal Cancer Expressing Wild-type KRAS and Who Had Progressed ≥ 6 Months After the Last Dose of the First Line Chemotherapy|
- Objective Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- disease control rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- duration of response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- time to response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- progression-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- time to progression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- time to treatment failure [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- duration of stable disease [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Incidence of adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2009|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Drug: Panitumumab + FOLFIRI
This is a Phase II, single-arm, multi-centre study. Patients with metastatic colorectal cancer expressing wild type KRAS will be screened for this trial. KRAS mutation status will be assessed before inclusion and only WILD-TYPE-KRAS subjects will be included. Eligible subjects will be enrolled and treated with combination therapy consisting of Panitumumab and FOLFIRI as second line treatment.
Eligible patients must not have progressed on or within 6 months after receiving first line chemotherapy based on fluoropyrimidines and oxaliplatin (prior adjuvant chemotherapy based on fluoropyrimidine is permitted). Only one previous chemotherapy regimen is permitted. Progression after 6 months receiving first line chemotherapy regimen, should be imaging-based.
Tumor response assessment will be performed by the investigator per the modified Response Evaluation Criteria in Solid Tumors (m-RECIST). Subjects will be evaluated for tumor response every 6 weeks ± 1 week the first 24 weeks and every 8 weeks thereafter (per the modified-RECIST criteria) until progression disease (PD) or withdrawal from the trial. Responding disease will be confirmed no less than 28 days after the criteria for response are first met. Subjects with symptoms suggestive of progression disease(PD) should be evaluated for tumor progression at the time the symptoms occur.
All subjects who permanently discontinue the treatment for any reason, will undergo a safety follow-up assessment 30 days ± 7 days after the last treatment dose Subjects will be followed for disease status and subsequent cancer therapy. All subjects who discontinue all the treatment before disease progression (eg, due to unacceptable toxicities) are followed for progression free survival (PFS) (eg, radiographic tumor assessments) every 12 weeks ± 14 days until disease progression or the end of study (unless the reason for study discontinuation is fully withdrawn consent). After disease progression, all subjects are followed every 12 weeks ± 14 days from the safety follow-up visit until the end of study (approximately 52 weeks after the last subject is enrolled).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01144195
|Associació Catalana per la Recerca Oncològica i les Seves Implicacions Sanitaries i Socials|
|Barcelona, Spain, 08021|
|Study Chair:||Carles Pericay, MD PhD||Corporació Sanitaria Parc Taulí, Sabadell (Spain)|
|Principal Investigator:||Ferran Losa, Dr.||Hospital General de l'Hospitalet|
|Principal Investigator:||Pilar Vicente, Dra.||Hospital General de Granollers|
|Principal Investigator:||Hermini Manzano, Dr.||Hospital Son Dureta|
|Principal Investigator:||Juan Manuel Campos, Dr.||Hospital Arnau de Vilanova (Valencia)|
|Principal Investigator:||Joan Manel Gasent, Dr.||Hospital de Denia|
|Principal Investigator:||Enrique Barrajón, Dr.||Clínica de Benidorm|
|Principal Investigator:||Inma Guasch, Dra.||Hospital General de Manresa|
|Principal Investigator:||Antonia Salud, Dra.||Hospital Arnau de Vilanova (Lleida)|
|Principal Investigator:||Miquel Nogué, Dr.||Hospital General de Vic|
|Principal Investigator:||Inés Cabezas, Dra.||Hospital Sant Joan de Reus|
|Principal Investigator:||Jordi Alfaro, MD||Consorci Sanitari de Terrassa|