Cetuximab for Elderly Patients With mCRC

NCT01718808 | Terminated Phase 2

• 1 other identifier: SAKK 41/10
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 14

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).

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer; KRAS; BRAF; Wild-type Metastatic; Cetuximab; Capecitabine; Phase II Trial; Elderly Patients

Outcome Measures

Primary Outcomes (1)

• Progression free survival in week 12

  A progression event is defined as (whichever occurs first): * Progressive disease (PD) assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Death of any cause * Starting of second line treatment * No tumor assessment 85 days (+/- 7 days) after registration which shows stabilisation or response Patients without tumor assessment at week 12 but with a later assessment showing absence of progression without subsequent treatment will be counted as a progression free at week 12

  in week 12

Secondary Outcomes (6)

• Quality of life (QL)

  Baseline, in week 7, 13 and 19

• Adverse events (CTCAE v 4.0)

  Adverse events are assessed by Common terminology criteria for adverse events (CTCAE) v4.0. From randomization until 30 days after end of treatment (estimated up to 2 years).

• Overall Response (OR)

  Before start of treatment. In week 13 and every 12 weeks up to 2 years.

• Progression free survival (PFS)

  PFS will be calculated sustained from randomization until documented PD or death, whichever occurs first (estimated up to 2 years).

• Overall Survival (OS)

  Overall survival will be calculated from randomization until death (estimated up to 2 years).

Study Arms (2)

Arm A: Cetuximab

ACTIVE COMPARATOR

Cetuximab 500 mg/m2 every 2 weeks

Drug: Cetuximab

Arm B: Cetuximab and Capecitabine

ACTIVE COMPARATOR

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

Drug: Cetuximab; Drug: Capecitabine

Interventions

Cetuximab DRUG

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

Also known as: Erbitux

Arm A: Cetuximab; Arm B: Cetuximab and Capecitabine

Capecitabine 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

Also known as: Xeloda

Arm B: Cetuximab and Capecitabine

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (14)

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Hopital Fribourgeois

Fribourg, 1708, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6000, Switzerland

Location

Kantonsspital Muensterlingen

Muensterlingen, 8596, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

SpitalSTS AG Simmental-Thun-Saanenland

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, CH-8400, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

Klinik Hirslanden

Zurich, CH-8032, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Dirk Kienle, MD

  Kantonsspital Graubünden

  STUDY CHAIR

• Roger von Moos, MD

  Kantonsspital Graubünden

  STUDY CHAIR

• Ralph Winterhalder, MD

  Luzerner Kantonsspital

  STUDY CHAIR

• Dieter Köberle, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 31, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2017
• Last Updated: January 24, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (14)