Panitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer

Amgen154 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

154

Conditions

Metastatic Colorectal Cancer

Interventions

PanitumumabDRUG

Administered by intravenous infusion

FOLFIRIDRUG

FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m², leucovorin 400 mg/m², 5-fluorouracil bolus 400 mg/m², 5-fluorouracil infusion 2400 mg/m².

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Objective Response Rate

Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments are based on investigator review of scans using modified Response Evaluation Criteria in Solid Tumors (RECIST) V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or progressive disease (PD) and no new lesions.

Time frame: 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

Objective Response by 17 Weeks

The percentage of participants with a best response of complete response or partial response by Week 17. Disease assessments are based on investigator review of scans using modified RECIST V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders.

Time frame: Up to Week 17

Disease Control Rate

The percentage of participants whose best response was either a complete or partial response or stable disease, based on modified RECIST v1.0 criteria as assessed by the Investigator. Stable diease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of existing non-target lesions and no new lesions, or, the persistence of 1 or more non-target lesions not qualifying for either CR or PD if no target lesions were identified at Baseline.

Time frame: 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

Data from ClinicalTrials.gov

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Duration of Response

Duration of response was calculated only for those participants who had a confirmed complete or partial response, and is defined as the time from first confirmed response to first observed progression. For participants who responded and did not progress by the analysis data cut-off date, duration of response was censored at their last evaluable disease assessment date. Duration of response was analyzed using the Kaplan-Meier method.

Time frame: 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.

Time to Initial Objective Response

Time to response is the time from the date of enrollment to the date of first confirmed complete or partial response. Participants with a best response of stable disease at the analysis data cut-off date were censored at their last assessment of SD and participants with all other categories of best response were censored at the maximum observed time to a first confirmed response among all responders. Time to initial objective response was analyzed using Kaplan-Meier methods.

Time frame: 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.

Progression-free Survival

Progression-free survival is the time from the date of enrollment to the date of first observed progression or death, whichever comes first. Participants who were alive and did not progress by the analysis data cut-off date were censored at the last evaluable disease assessment date. Progression-free survival was analyzed using Kaplan-Meier methods.