Cetuximab for Elderly Patients With mCRC
Primary Purpose
Metastatic Colorectal Cancer
Status
Terminated
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Cetuximab
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metastatic Colorectal Cancer, KRAS, BRAF, Wild-type Metastatic, Cetuximab, Capecitabine, Phase II Trial, Elderly Patients
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
Sites / Locations
- Universitaetsspital-Basel
- Inselspital, Bern
- Spitalzentrum Biel
- Hopital Fribourgeois
- Hopital Cantonal Universitaire de Geneve
- Centre Hospitalier Universitaire Vaudois
- Kantonsspital Luzern
- Kantonsspital Muensterlingen
- Kantonsspital - St. Gallen
- SpitalSTS AG Simmental-Thun-Saanenland
- Kantonsspital Winterthur
- Klinik Hirslanden
- UniversitaetsSpital Zuerich
- Stadtspital Triemli
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Arm A: Cetuximab
Arm B: Cetuximab and Capecitabine
Arm Description
Cetuximab 500 mg/m2 every 2 weeks
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
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Quality of life (QL)
Adverse events (CTCAE v 4.0)
Overall Response (OR)
Progression free survival (PFS)
Overall Survival (OS)
Overall treatment utility (OTU) (predefined composite endpoint including clinical benefit, tolerability and acceptability of the treatment)
Full Information
NCT ID
NCT01718808
First Posted
October 22, 2012
Last Updated
January 23, 2017
Sponsor
Swiss Group for Clinical Cancer Research
1. Study Identification
Unique Protocol Identification Number
NCT01718808
Brief Title
Cetuximab for Elderly Patients With mCRC
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
FU for 3 years from randomization as initially planned is stopped as we do not expect any changes to the endpoints in the future after one year of FU.
Study Start Date
November 2012 (Actual)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Metastatic Colorectal Cancer, KRAS, BRAF, Wild-type Metastatic, Cetuximab, Capecitabine, Phase II Trial, Elderly Patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Cetuximab
Arm Type
Active Comparator
Arm Description
Cetuximab 500 mg/m2 every 2 weeks
Arm Title
Arm B: Cetuximab and Capecitabine
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression free survival in week 12
Description
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
Time Frame
in week 12
Secondary Outcome Measure Information:
Title
Quality of life (QL)
Time Frame
Baseline, in week 7, 13 and 19
Title
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).
Title
Overall Response (OR)
Time Frame
Before start of treatment. In week 13 and every 12 weeks up to 2 years.
Title
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).
Title
Overall Survival (OS)
Time Frame
Overall survival will be calculated from randomization until death (estimated up to 2 years).
Title
Overall treatment utility (OTU) (predefined composite endpoint including clinical benefit, tolerability and acceptability of the treatment)
Time Frame
Until week 19.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk Kienle, MD
Organizational Affiliation
Kantonsspital Graubünden
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Roger von Moos, MD
Organizational Affiliation
Kantonsspital Graubünden
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ralph Winterhalder, MD
Organizational Affiliation
Luzerner Kantonsspital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Dieter Köberle, MD
Organizational Affiliation
Cantonal Hospital of St. Gallen
Official's Role
Study Chair
Facility Information:
Facility Name
Universitaetsspital-Basel
City
Basel
ZIP/Postal Code
CH-4031
Country
Switzerland
Facility Name
Inselspital, Bern
City
Bern
ZIP/Postal Code
CH-3010
Country
Switzerland
Facility Name
Spitalzentrum Biel
City
Biel
ZIP/Postal Code
CH-2501
Country
Switzerland
Facility Name
Hopital Fribourgeois
City
Fribourg
ZIP/Postal Code
1708
Country
Switzerland
Facility Name
Hopital Cantonal Universitaire de Geneve
City
Geneva
ZIP/Postal Code
CH-1211
Country
Switzerland
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Kantonsspital Luzern
City
Luzern
ZIP/Postal Code
6000
Country
Switzerland
Facility Name
Kantonsspital Muensterlingen
City
Muensterlingen
ZIP/Postal Code
8596
Country
Switzerland
Facility Name
Kantonsspital - St. Gallen
City
St. Gallen
ZIP/Postal Code
CH-9007
Country
Switzerland
Facility Name
SpitalSTS AG Simmental-Thun-Saanenland
City
Thun
ZIP/Postal Code
3600
Country
Switzerland
Facility Name
Kantonsspital Winterthur
City
Winterthur
ZIP/Postal Code
CH-8400
Country
Switzerland
Facility Name
Klinik Hirslanden
City
Zurich
ZIP/Postal Code
CH-8032
Country
Switzerland
Facility Name
UniversitaetsSpital Zuerich
City
Zurich
ZIP/Postal Code
CH-8091
Country
Switzerland
Facility Name
Stadtspital Triemli
City
Zürich
ZIP/Postal Code
8063
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
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Cetuximab for Elderly Patients With mCRC
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