Study of Panitumumab-Capecitabine-Oxaliplatin In Wild-Type K-Ras Metastatic Colorectal Cancer Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether panitumumab in combination with capecitabine/oxaliplatin are effective as first-line treatment in wild-type k-ras, metastatic colorectal cancer patients.

Detailed Description
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This is a single-arm trial in which previously untreated, wild-type k-ras metastatic colorectal cancer patients will receive therapy with the combination of panitumumab with capecitabine and oxaliplatin. During the treatment period of 6 cycles, subjects with evidence of complete response, partial response or stable disease will continue to receive the combination of chemotherapy with panitumumab until disease progression, unacceptable toxicity or withdrawal of consent. Those patients with disease stabilization who are not appropriate for chemotherapy may continue with panitumumab alone. Patients with disease progression will be discontinued from chemotherapy and panitumumab and will be followed every 3 months after the last drug administration until death. Tumor response will be assessed according to the RECIST criteria (investigator's read of scans), every 6 weeks through week 18 and every 3 months thereafter, until disease progression. Disease progression will also be evaluated radiographically at the time of clinical suspicion of progression.

Official Title
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A SINGLE-ARM, MULTICENTER, PHASE II STUDY OF PANITUMUMAB IN COMBINATION WITH CAPECITABINE / OXALIPLATIN IN FIRST-LINE, WILD-TYPE K-RAS METASTATIC COLORECTAL CANCER PATIENTS.

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to comprehend and sign an informed consent Aged 18 years or more Histologically or cytologically-confirmed metastatic adenocarcinoma of the colon and/or rectum Measurable disease according to the RECIST criteria Eastern Cooperative Oncology Group (ECOG) status of 0-2 Non-mutated k-ras gene (k-ras status will be assessed by DNA sequencing in codons 12 and 13) Haematologic function: ANC >1.5 x 109/L, Leucocyte count >3000/mm3, Haemoglobin >10g/ d L, PLT >100 x 109/ L Renal function: serum creatinine ≤1.5xUNL or creatinine clearance > 50ml/min Hepatic function: Total bilirubin ≤ 1.5 time the upper normal limit (UNL) ASAT ≤ 2.5xUNL in absence of liver metastases, or ≤5xUNL in presence of liver metastases ALAT ≤ 2.5xUNL in absence of liver metastases, or ≤5xUNL in presence of liver metastases Metabolic function: Magnesium ≥ lower limit of normal. Calcium ≥ lower limit of normal. Exclusion Criteria: Central nervous system metastases Prior therapy for metastatic disease Adjuvant chemotherapy for the last 6 months Prior anti-EGFR therapy or treatment with EGFR tyrosine kinase inhibitors Prior radiotherapy within 30 days from enrollment Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) <=1 year before enrollment History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan. Inflammatory bowel disease or chronic diarrhea Dihydropyrimidine deficiency Positive test for HIV infection, hepatitis C infection, chronic active hepatitis B infection Any kind of disorder compromising the ability of the patient to give informed consent Any investigational agent within 30 days prior to initiation of the study Any surgical procedure within 28 days prior to initiation of the study Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. Female subject in childbearing age with a positive pregnancy test at screening or before initiation of study treatment. Subject (male or female) not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panitumumab,capecitabine,oxaliplatin<br>Panitumumab will be administered by IV infusion on day 1 of each 3-week cycle prior to the administration of chemotherapy. The starting panitumumab dose is 9 mg/kg. Oxaliplatin 130 mg/m2 IV infusion over 2 hours on Day 1 Capecitabine 2000 mg/m2 divided in two doses, orally, on Days 1 - 14 | Drug: panitumumab<br>* Panitumumab will be administered by IV infusion on day 1 of each 3-week cycle prior to the administration of chemotherapy. The starting panitumumab dose is 9 mg/kg. Subjects with evidence of complete response, partial response or stable disease will continue to receive the combination of chemotherapy with panitumumab until disease progression, unacceptable toxicity or withdrawal of consent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response | Response will be evaluated using the RECIST criteria. Response rates will be presented as counts and proportions along with 95% exact confidence intervals. An Objective Response is defined as either a Complete Response or a Partial Response. Analysis will be performed in the intent-to-treat population, i.e. all eligible patients enrolled in the study. | Tumor response will be assessed every 6 weeks through week 18 and every 3 months thereafter, until disease progression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS will be calculated from the date of enrolment to the date of death or last contact | 24 months | 
| Progression-Free Survival(PFS) | PFS will be calculated from the date of enrolment to the date of disease progression, or death, or last contact. Deaths without a documented progression will be treated as events at the time of death for the PFS analysis. Time to event distributions will be estimated using the Kaplan-Meier method. | Tumor response will be assessed every 6 weeks through week 18 and every 3 months thereafter, until disease progression. | 
| Adverse Events (AE)of all participants will be recorded and assessed upon signature of the informed consent form, until 30 days after the last administration of study treatment. | Adverse Events will be graded according to the NCI CTCAE v3.0 criteria and will be reported in a frequency table according to the highest severity grade observed per patient | 18 months | 
| Economic evaluation | The purpose of economic evaluation will be to estimate the total treatment cost of therapy and its componenents from perspective of the health care system and payers. Thus, all resources consumed will be valued to get an idea of the financial implications of therapy. | 18 months |