Cetuximab for Elderly Patients With mCRC

NCT ID: NCT01718808

Last Updated: 2017-01-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2017-01-31

Brief Summary

OBJECTIVE: The objective of the trial is to judge on the benefit obtained by an upfront cetuximab treatment delivered as monotherapy or as part of a combination treatment with capecitabine in vulnerable elderly patients selected for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type and B-type Raf kinase (BRAF) wild-type metastatic colorectal cancer (mCRC).

Detailed Description

Primary endpoint: If in a treatment arm the number of patients alive and without progression at 12 weeks is 17 or more, this arm will be considered promising, otherwise not promising. Additionally, a two-sided 95% confidence interval for the difference in Progression free survival (PFS) rates between the two arms will be calculated.

Secondary endpoints and patient characteristics:

• Laboratory values may be expressed as the absolute values (continuous variables) or/and as grading (ordinal categorical variables).
• Generally for each categorical variable the results will be summarized by frequencies and percentages. For response rates 95% Clopper-Pearson confidence intervals will be calculated.
• For each adverse event, the results will be summarized by frequencies and percentages of different grades among all cycles as well as by frequencies and percentages of the within-patient worst grades
• For each continuous variable the results will be summarized by descriptive statistics.
• Time-to-event variables will be presented by Kaplan-Meier curves and summarized by medians and 95% confidence intervals.
• All analysis will be done by treatment arm.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Cetuximab

Cetuximab 500 mg/m2 every 2 weeks

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: DRUG

Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity

Arm B: Cetuximab and Capecitabine

Cetuximab 500 mg/m2 every 2 weeks plus Capecitabine 1000 mg/m2 (*) bid d1-14 every 3 weeks

• 750 mg/m2 if creatinine-clearance 30-50 ml/min

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: DRUG

Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity

Capecitabine

Intervention Type: DRUG

Capecitabine 1000 mg/m2 bid p.o. (750 mg/m2 if creatinine clearance 30-50 ml/min according to Cockroft-Gault formula, on days 1-14 every 3 weeks, restart on day 22

Interventions

Cetuximab

Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity

Intervention Type: DRUG

Capecitabine

Capecitabine 1000 mg/m2 bid p.o. (750 mg/m2 if creatinine clearance 30-50 ml/min according to Cockroft-Gault formula, on days 1-14 every 3 weeks, restart on day 22

Intervention Type: DRUG

Other Intervention Names

Erbitux; Xeloda

Eligibility Criteria

Inclusion Criteria

• Patient has given written informed consent before any trial specific treatment
• Histological proven diagnosis of colorectal cancer, metastatic or inoperable advanced, not amenable to curative therapy
• Measurable disease, defined as at least one lesion (outside of irradiated areas) that can be measured in at least one dimension as ≥ 10 mm (≥ 15 mm in case of lymph nodes) according to RECIST v1.1
• Tumour with wild-type KRAS and wild-type BRAF gene
• No previous systemic chemotherapy for metastatic disease (previous adjuvant chemotherapy is allowed if completed >6 months before randomization, previous rectal radio-chemo therapy if completed >1 month before randomization)
• WHO performance status 0 or 1
• Age >75 years; or: age ≥ 70 years with at least one of the following factors:
• Any functional dependence as measured by Instrumental Activities of Daily Life (IADL). Significant comorbidity according to the Cumulative Illness Rating Scale for geriatric patients (CIRS-G; any severe comorbidity > grade 3 or a total score > 5 qualifies)
• Neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
• Bilirubin ≤ 2.0 x Upper Limit of Normal (ULN) (unless known Gilbert-Meulengracht syndrome), aspartate aminotransferase (AST)<2.5xULN
• Calculated creatinine clearance ≥ 30 ml/min. (according to the formula of Cockcroft-Gault)
• Patient is able to swallow oral medication
• Baseline Quality of Life forms have been completed

Exclusion Criteria

• Documented or suspected cerebral and/or leptomeningeal metastases (no cerebral baseline imaging required in asymptomatic patients)
• Risk of rapid deterioration due to tumor symptoms or tumor complications
• Synchronous or prior malignancy other than adequately treated non-melanomatous skin cancer or in situ carcinoma of the cervix, other malignancies unless disease free > 2 years
• Prior anti-EGFR (Epidermal Growth Factor Receptor) antibody therapy
• Severe or uncontrolled cardiovascular disease (e.g. acute coronary syndromes, cardiac failure NYHA (New York Heart Association) III or IV, clinically relevant myopathy, history of myocardial infarction within the last 12 months, significant arrhythmias)
• Concurrent severe uncontrolled medical illness (judged by the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled infection, uncontrolled diabetes mellitus, active autoimmune disease)
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drug
• Definite contraindications for the use of corticosteroids or antihistamines as premedication
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome or history of inflammatory intestinal disease, or other disease which could alter drug absorption
• Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out QL forms, or interfering with compliance with oral drug intake
• Any concomitant drugs contraindicated for use with the trial drugs according to the Swissmedic approved product information
• Concurrent treatment with other experimental drugs or other anti-cancer therapy and/or treatment in a clinical trial within 30 days prior to randomization

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dirk Kienle, MD

Role: STUDY_CHAIR

Kantonsspital Graubünden

Roger von Moos, MD

Role: STUDY_CHAIR

Kantonsspital Graubünden

Ralph Winterhalder, MD

Role: STUDY_CHAIR

Luzerner Kantonsspital

Dieter Köberle, MD

Role: STUDY_CHAIR

Cantonal Hospital of St. Gallen

Locations

Universitaetsspital-Basel

Basel, , Switzerland

Inselspital, Bern

Bern, , Switzerland

Spitalzentrum Biel

Biel, , Switzerland

Hopital Fribourgeois

Fribourg, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Luzern

Lucerne, , Switzerland

Kantonsspital Muensterlingen

Muensterlingen, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

SpitalSTS AG Simmental-Thun-Saanenland

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Stadtspital Triemli

Zurich, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

SAKK 41/10

Identifier Type: -

Identifier Source: org_study_id