Clinical trial NCT00508404: Panitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer
Official title: A Single Arm Multicentre Phase II Study of Panitumumab in Combination With Irinotecan/5-fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2007-07-30
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To estimate the effect of KRAS mutation status (Wild-type versus Mutant) on objective response rate and other measures of efficacy for patients treated with panitumumab in combination with a chemotherapy regimen of irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line therapy for metastatic colorectal cancer (mCRC).


Eligibility criteria: Inclusion Criteria:

* Diagnosed with histologically- or cytologically-confirmed metastatic adenocarcinoma of the colon and/or rectum.
* Measurable disease according to modified RECIST guidelines.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
* Paraffin-embedded tissue or unstained tumour slides from primary or metastatic tumour available for central lab analysis.
* Adequate haematologic, renal, hepatic and metabolic function.

Exclusion Criteria:

* Central nervous system metastases.
* Prior systemic therapy for the treatment of metastatic colorectal carcinoma with the exception of adjuvant fluoropyrimidine-based chemotherapy given at least six months prior to initiating study treatment.
* Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (e.g. cetuximab) or treatment with small molecule EGFr tyrosine kinase inhibitors (e.g. erlotinib).
* Prior radiotherapy within 14 days prior to screening, and for which all signs of early radiological toxicity have not abated.
* Significant cardiovascular disease including unstable angina or myocardial infarction within six months before initiating study treatment or a history of ventricular arrhythmia.
* History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computed tomography (CT scan.
* Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as \> 4 loose stools per day).
* History of Gilbert's syndrome or dihydropyrimidine deficiency.
* Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection.
* Any investigational agent within 30 days before initiation of study treatment.
* Must not have had a major surgical procedure within 28 days prior to initiation of study treatment.
* Subject who is pregnant or breast-feeding.
* Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the course of the study and for six months after the last study drug administration for women, and one month for men.

  * Other protocol specified criteria and specific details may apply.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks
Secondary outcomes:
measure: Objective Response by 17 Weeks
timeFrame: Up to Week 17
measure: Disease Control Rate
timeFrame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks
measure: Duration of Response
timeFrame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks.
measure: Time to Initial Objective Response
timeFrame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks.
measure: Progression-free Survival
timeFrame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
measure: Time to Disease Progression
timeFrame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
measure: Duration of Stable Disease
timeFrame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks.
measure: Time to Treatment Failure
timeFrame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
measure: Time to Disease Relapse Following Surgical Intervention
timeFrame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
measure: Resection Rate
timeFrame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks.
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Kohne CH, Hofheinz R, Mineur L, Letocha H, Greil R, Thaler J, Fernebro E, Gamelin E, Decosta L, Karthaus M. First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer. J Cancer Res Clin Oncol. 2012 Jan;138(1):65-72. doi: 10.1007/s00432-011-1061-6. Epub 2011 Sep 30.
citation: Thaler J, Karthaus M, Mineur L, Greil R, Letocha H, Hofheinz R, Fernebro E, Gamelin E, Banos A, Kohne CH. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study. BMC Cancer. 2012 Sep 29;12:438. doi: 10.1186/1471-2407-12-438.
citation: Taieb J, Geissler M, Rivera F, Karthaus M, Wilson R, Loupakis F, Price T, Tracy M, Burdon P, Peeters M. Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials. Clin Colorectal Cancer. 2019 Dec;18(4):245-256.e5. doi: 10.1016/j.clcc.2019.07.009. Epub 2019 Jul 29.
citation: Kohne CH, Karthaus M, Mineur L, Thaler J, Van den Eynde M, Gallego J, Koukakis R, Berkhout M, Hofheinz RD. Impact of Primary Tumour Location and Early Tumour Shrinkage on Outcomes in Patients with RAS Wild-Type Metastatic Colorectal Cancer Following First-Line FOLFIRI Plus Panitumumab. Drugs R D. 2019 Sep;19(3):267-275. doi: 10.1007/s40268-019-0278-8.