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

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.

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: panitumumab

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 Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens "Hippokratio", 2nd Dept of Internal Medicine
  • Athens, Greece, 11527
    • Sotiria General Hospital, 3rd Dept of Medicine, Oncology Unit
  • Athens, Greece, 11528
    • General Peripheral Hospital of Athens "Alexandra"
  • Athens, Greece, 14564
    • Agii Anargiri Cancer Hospital, Oncology Dept
  • Athens, Greece, 15123
    • Hygeia Hospital, 2nd Dept of Medical Oncology
  • Athens, Greece, 15123
    • Hygeia Hospital, 3rd Dept of Medical Oncology
  • Athens, Greece, 18547
    • Metropolitan Hospital, 1st Dept of Medical Oncology
  • Athens, Greece, 18547
    • Metropolitan Hospital, 2nd Dept of Medical Oncology
  • Chania, Greece, 73100
    • Chania General Hospital
  • Ioannina, Greece, 45110
    • Ioannina University Hospital, Dept of Medical Oncology
  • Patras, Greece, 26500
    • Rio University Hospital, Dept of Oncology
  • Thessaloniki, Greece, 56429
    • Papageorgiou General Hospital, Dept of Medical Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Panitumumab,capecitabine,oxaliplatin; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hellenic Cooperative Oncology Group
• Investigators: Study Chair: Dimitrios Pectasides, Professor, General Hospital of Athens"Hippokratio", 2nd Dept of Internal Medicine

Publications and helpful links

General Publications

• Papaxoinis G, Kotoula V, Giannoulatou E, Koliou GA, Karavasilis V, Lakis S, Koureas A, Bobos M, Chalaralambous E, Daskalaki E, Chatzopoulos K, Tsironis G, Pazarli E, Chrisafi S, Samantas E, Kaklamanos IG, Varthalitis I, Konstantara A, Syrigos KN, Pentheroudakis G, Pectasides D, Fountzilas G. Phase II study of panitumumab combined with capecitabine and oxaliplatin as first-line treatment in metastatic colorectal cancer patients: clinical results including extended tumor genotyping. Med Oncol. 2018 May 31;35(7):101. doi: 10.1007/s12032-018-1160-1.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: September 29, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimate): October 6, 2010

Study Record Updates

• Last Update Posted (Estimate): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Panitumumab
• Other Study ID Numbers: HE 6A/09; 2009-012655-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No