Clinical trial NCT01215539: Study of Panitumumab-Capecitabine-Oxaliplatin In Wild-Type K-Ras Metastatic Colorectal Cancer Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Hellenic Cooperative Oncology Group
Sponsor class: OTHER
First posted: 2010-10-06
Enrollment: 78
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response
timeFrame: Tumor response will be assessed every 6 weeks through week 18 and every 3 months thereafter, until disease progression.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 24 months
measure: Progression-Free Survival(PFS)
timeFrame: Tumor response will be assessed every 6 weeks through week 18 and every 3 months thereafter, until disease progression.
measure: 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.
timeFrame: 18 months
measure: Economic evaluation
timeFrame: 18 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: General Hospital of Athens "Hippokratio", 2nd Dept of Internal Medicine
city: Athens
country: Greece
facility: Sotiria General Hospital, 3rd Dept of Medicine, Oncology Unit
city: Athens
country: Greece
facility: General Peripheral Hospital of Athens "Alexandra"
city: Athens
country: Greece
facility: Agii Anargiri Cancer Hospital, Oncology Dept
city: Athens
country: Greece
facility: Hygeia Hospital, 2nd Dept of Medical Oncology
city: Athens
country: Greece
facility: Hygeia Hospital, 3rd Dept of Medical Oncology
city: Athens
country: Greece
facility: Metropolitan Hospital, 1st Dept of Medical Oncology
city: Athens
country: Greece
facility: Metropolitan Hospital, 2nd Dept of Medical Oncology
city: Chania
country: Greece
facility: Chania General Hospital
city: Ioannina
country: Greece
facility: Ioannina University Hospital, Dept of Medical Oncology
city: Patras
country: Greece
facility: Rio University Hospital, Dept of Oncology
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital, Dept of Medical Oncology
Study officials:
affiliation: General Hospital of Athens"Hippokratio", 2nd Dept of Internal Medicine
name: Dimitrios Pectasides, Professor
role: STUDY_CHAIR
References:
citation: 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.