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

Phase 2

Completed

• Conditions: Colorectal Cancer
• Interventions: Drug: panitumumab

• Registration Number: NCT01215539
• Lead Sponsor: Hellenic Cooperative Oncology Group

Brief Summary

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

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.

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-09-29
• Study First Submitted QC: 2010-10-05
• Study First Posted: 2010-10-06
• Primary Completion: 2014-08
• Study Completion: 2014-12
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-17
• Last Update Posted: 2015-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. Ability to comprehend and sign an informed consent

2. Aged 18 years or more

3. Histologically or cytologically-confirmed metastatic adenocarcinoma of the colon and/or rectum

4. Measurable disease according to the RECIST criteria

5. Eastern Cooperative Oncology Group (ECOG) status of 0-2

6. Non-mutated k-ras gene (k-ras status will be assessed by DNA sequencing in codons 12 and 13)

7. Haematologic function: ANC >1.5 x 109/L, Leucocyte count >3000/mm3, Haemoglobin >10g/ d L, PLT >100 x 109/ L

8. Renal function: serum creatinine ≤1.5xUNL or creatinine clearance > 50ml/min

9. 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

10. Metabolic function:

    • Magnesium ≥ lower limit of normal.
    • Calcium ≥ lower limit of normal.

Exclusion Criteria

1. Central nervous system metastases
2. Prior therapy for metastatic disease
3. Adjuvant chemotherapy for the last 6 months
4. Prior anti-EGFR therapy or treatment with EGFR tyrosine kinase inhibitors
5. Prior radiotherapy within 30 days from enrollment
6. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) <=1 year before enrollment
7. History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
8. Inflammatory bowel disease or chronic diarrhea
9. Dihydropyrimidine deficiency
10. Positive test for HIV infection, hepatitis C infection, chronic active hepatitis B infection
11. Any kind of disorder compromising the ability of the patient to give informed consent
12. Any investigational agent within 30 days prior to initiation of the study
13. Any surgical procedure within 28 days prior to initiation of the study
14. Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
15. Female subject in childbearing age with a positive pregnancy test at screening or before initiation of study treatment.
16. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Panitumumab,capecitabine,oxaliplatin	panitumumab	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

Primary Outcome Measures

Name	Time	Method
Objective Response	Tumor response will be assessed every 6 weeks through week 18 and every 3 months thereafter, until disease progression.	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	24 months	OS will be calculated from the date of enrolment to the date of death or last contact
Progression-Free Survival(PFS)	Tumor response will be assessed every 6 weeks through week 18 and every 3 months thereafter, until disease progression.	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.
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.	18 months	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
Economic evaluation	18 months	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.

Trial Locations

Locations (12)

General Hospital of Athens "Hippokratio", 2nd Dept of Internal Medicine; 🇬🇷 Athens, Greece

Rio University Hospital, Dept of Oncology; 🇬🇷 Patras, Greece

Hygeia Hospital, 3rd Dept of Medical Oncology; 🇬🇷 Athens, Greece

Metropolitan Hospital, 1st Dept of Medical Oncology; 🇬🇷 Athens, Greece

Ioannina University Hospital, Dept of Medical Oncology; 🇬🇷 Ioannina, Greece

Hygeia Hospital, 2nd Dept of Medical Oncology; 🇬🇷 Athens, Greece

General Peripheral Hospital of Athens "Alexandra"; 🇬🇷 Athens, Greece

Chania General Hospital; 🇬🇷 Chania, Greece

Sotiria General Hospital, 3rd Dept of Medicine, Oncology Unit; 🇬🇷 Athens, Greece

Metropolitan Hospital, 2nd Dept of Medical Oncology; 🇬🇷 Athens, Greece

Agii Anargiri Cancer Hospital, Oncology Dept; 🇬🇷 Athens, Greece

Papageorgiou General Hospital, Dept of Medical Oncology; 🇬🇷 Thessaloniki, Greece