Cetuximab for Elderly Patients With mCRC

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01718808
First received: October 22, 2012
Last updated: January 18, 2015
Last verified: January 2015
  Purpose

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).


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Cetuximab
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cetuximab Monotherapy and Cetuximab Plus Capecitabine as First-line Treatment in Elderly Patients With KRAS- and BRAF Wild-type Metastatic Colorectal Cancer. A Multicenter Phase II Trial

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Progression free survival in week 12 [ Time Frame: in week 12 ] [ Designated as safety issue: No ]

    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


Secondary Outcome Measures:
  • Quality of life (QL) [ Time Frame: Baseline, in week 7, 13 and 19 ] [ Designated as safety issue: No ]
  • Adverse events (CTCAE v 4.0) [ Time Frame: 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). ] [ Designated as safety issue: Yes ]
  • Overall Response (OR) [ Time Frame: Before start of treatment. In week 13 and every 12 weeks up to 2 years. ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) [ Time Frame: PFS will be calculated sustained from randomization until documented PD or death, whichever occurs first (estimated up to 2 years). ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Overall survival will be calculated from randomization until death (estimated up to 2 years). ] [ Designated as safety issue: No ]
  • Overall treatment utility (OTU) (predefined composite endpoint including clinical benefit, tolerability and acceptability of the treatment) [ Time Frame: Until week 19. ] [ Designated as safety issue: No ]

Estimated Enrollment: 78
Study Start Date: November 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A: Cetuximab
Cetuximab 500 mg/m2 every 2 weeks
Drug: Cetuximab
Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity
Other Name: Erbitux
Active Comparator: 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

Drug: Cetuximab
Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity
Other Name: Erbitux
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
Other Name: Xeloda

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.
  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718808

Locations
Switzerland
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Inselspital, Bern
Bern, Switzerland, CH-3010
Spitalzentrum Biel
Biel, Switzerland, CH-2501
Hopital Fribourgeois
Fribourg, Switzerland, 1708
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Luzern
Luzern, Switzerland, 6000
Kantonsspital Muensterlingen
Muensterlingen, Switzerland, 8596
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
SpitalSTS AG Simmental-Thun-Saanenland
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, CH-8400
Klinik Hirslanden
Zurich, Switzerland, CH-8032
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Stadtspital Triemli
Zürich, Switzerland, 8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: 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
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01718808     History of Changes
Other Study ID Numbers: SAKK 41/10
Study First Received: October 22, 2012
Last Updated: January 18, 2015
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
Metastatic Colorectal Cancer
KRAS
BRAF
Wild-type Metastatic
Cetuximab
Capecitabine
Phase II Trial
Elderly Patients

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Capecitabine
Cetuximab
Fluorouracil
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 07, 2015