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Colorectal Cancer (CRC) Cetuximab Elderly Frail

Primary Purpose

Colorectal Cancer Metastatic

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cetuximab
5-fluorouracil
leucovorin
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring KRAS Wild Type, Frail Elderly, QLQ-C30, QLQ-ELD14, CGA, EGFR, Cetuximab, 5-FU

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pathologically confirmed metastatic colorectal cancer
  • Measurable disease according to RECIST V1.1
  • Histological local review and analysis of KRAS
  • Age ≥ 80 or ≥ 70 in combination with functional restrictions defined as limitation in at least 2 of 8 IADL
  • WHO performance status 0, 1 or 2
  • Adequate bone marrow reserves, hepatic function & renal function
  • Normal 12 lead ECG without clinically significant abnormalities
  • Written informed consent before randomization according to ICH/EU GCP, and local, national and international regulations

Exclusion Criteria:

  • Prior systemic chemotherapy for metastatic disease
  • Previous exposure to EGFR or VEGF/VEGFR targeted therapy
  • Patients may have received chemotherapy in the adjuvant or neoadjuvant setting (CRC). The treatment-free interval should be 6 months or more from the end of (neo-)adjuvant therapy
  • Previous radiotherapy, either in the adjuvant setting or for the treatment of bone metastases, is allowed provided that the measurable lesions are outside the radiation fields
  • Persistence of clinically relevant treatment-related toxicities from previous chemotherapy and/or radiotherapy (adjuvant or neo-adjuvant setting)
  • Treatment with other investigational drugs or treatment in another clinical trial within the past four weeks before start of treatment or concomitantly with this trial
  • Known alcohol or drug abuse
  • Clinically significant cardiovascular disease
  • Evidence of uncontrolled medical comorbidities despite adequate treatment
  • Patients who have suffered a cerebrovascular accident or transient ischemic attack within the past 12 months
  • History, within the past 5 years, of malignancies other than CRC
  • Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and followup schedule

Sites / Locations

  • AZ Turnhout - Campus Sint Elisabeth
  • Bank Of Cyprus Oncology Centre
  • Hospital General Vall D'Hebron

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

5-fluorouracil/leucovorin plus cetuximab

5-fluorouracil/leucovorin alone

Arm Description

Outcomes

Primary Outcome Measures

Progression free survival
Progression will be defined according to the "RECIST V1.1"

Secondary Outcome Measures

Overall Survival
Response Rate
according to the RECIST V1.1
Change in Instrumental Activities of Daily Living (IADL) score
Change in G8 geriatric assessment screening tool
Change in social situation
Score of Quality of Life (EORTC-QLQ C30 and QLQ-ELD14)
Occurrence of adverse events
Adverse events will be graded according to the "Common Terminology Criteria for Adverse events" CTCAE,version 4.0.
Health Economy assessments
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by G8 instrument
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by Instrumental Activities of Daily Life (IADL) questionnaire
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by social situation questionnaire

Full Information

First Posted
January 27, 2012
Last Updated
June 9, 2016
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT01522612
Brief Title
Colorectal Cancer (CRC) Cetuximab Elderly Frail
Official Title
Treatment of Patients With KRAS Wild Type Advanced Colorectal Cancer (CRC) With 5-Fluorouracil (5-FU) or 5- FU Plus an Epidermal Growth Factor Receptor (EGFR) Inhibitor (Cetuximab) Based on a Comprehensive Geriatric Assessment (CGA).
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
poor accrual
Study Start Date
April 2013 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
OBJECTIVE: The principal objective of the trial is to evaluate whether the addition of cetuximab associated with 5-fluorouracil in elderly patients with KRAS wild type advanced colorectal cancer (CRC) prolongs Progression Free Survival, compared with 5-fluorouracil alone.
Detailed Description
The primary efficacy analyses will be performed on the Intention-to-treat population. The safety analyses will be performed on the Safety population. Median PFS and OS in each treatment arm with its 95% CI, estimated by the Kaplan-Meier technique Response rates by treatment arm with their exact 95% CI IADL sum score, G8 sum score and social situation by treatment arm at baseline and at each timepoint of assessment QoL scores from the EORTC QLQ-C30 and QLQ-ELD14 modules by treatment arm at baseline and at each timepoint of assessment Safety data by treatment arm in the Safety population. Worst toxicity grade over all cycles according to the CTCAE criteria version 4.0 by treatment arm. Pharmaco-economics evaluation Summary of proposed Phase II trial characteristics: Total number of randomized patients: 150. Total number of events at phase II analysis for primary endpoint: 110. Total number of patients screened over the phase II: 250. Total number of patients treated with cetuximab for the Phase II study: 75. Maximum study duration: 19 months. In the present study, HRQoL is an important secondary endpoint. The objective of the HRQoL data collection in this Phase II trial is to assess the impact of the addition of cetuximab on patients' HRQoL during treatment. The hypothesis is that there will be no difference in patients' HRQoL between both treatment arms during treatment. The HRQoL domains (from the EORTC QLQ-C30 module) which are expected to be affected by treatment (to the same extent in both arms) are Global health status, Fatigue, Pain and Stool habits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic
Keywords
KRAS Wild Type, Frail Elderly, QLQ-C30, QLQ-ELD14, CGA, EGFR, Cetuximab, 5-FU

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
5-fluorouracil/leucovorin plus cetuximab
Arm Type
Experimental
Arm Title
5-fluorouracil/leucovorin alone
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
500 mg/m2 on day 1, Every 14 days Intravenously
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Other Intervention Name(s)
5-FU
Intervention Description
Every 2 weeks, 400 mg/m2 on day 1; 2400 mg/m2 from day 1 to day 3, intravenously
Intervention Type
Drug
Intervention Name(s)
leucovorin
Other Intervention Name(s)
Folinic Acid
Intervention Description
Every 2 weeks, Racemic leucovorin 200 mg/m2 or l-leucovorin 100 mg/m2 on day 1, intravenously
Primary Outcome Measure Information:
Title
Progression free survival
Description
Progression will be defined according to the "RECIST V1.1"
Time Frame
19 months from first patient in
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
19 months from first patient in
Title
Response Rate
Description
according to the RECIST V1.1
Time Frame
19 months from first patient in
Title
Change in Instrumental Activities of Daily Living (IADL) score
Time Frame
19 months from first patient in
Title
Change in G8 geriatric assessment screening tool
Time Frame
19 months from first patient in
Title
Change in social situation
Time Frame
19 months from first patient in
Title
Score of Quality of Life (EORTC-QLQ C30 and QLQ-ELD14)
Time Frame
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Title
Occurrence of adverse events
Description
Adverse events will be graded according to the "Common Terminology Criteria for Adverse events" CTCAE,version 4.0.
Time Frame
19 months from first patient in
Title
Health Economy assessments
Time Frame
19 months from first patient in
Title
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by G8 instrument
Time Frame
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Title
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by Instrumental Activities of Daily Life (IADL) questionnaire
Time Frame
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Title
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by social situation questionnaire
Time Frame
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically confirmed metastatic colorectal cancer Measurable disease according to RECIST V1.1 Histological local review and analysis of KRAS Age ≥ 80 or ≥ 70 in combination with functional restrictions defined as limitation in at least 2 of 8 IADL WHO performance status 0, 1 or 2 Adequate bone marrow reserves, hepatic function & renal function Normal 12 lead ECG without clinically significant abnormalities Written informed consent before randomization according to ICH/EU GCP, and local, national and international regulations Exclusion Criteria: Prior systemic chemotherapy for metastatic disease Previous exposure to EGFR or VEGF/VEGFR targeted therapy Patients may have received chemotherapy in the adjuvant or neoadjuvant setting (CRC). The treatment-free interval should be 6 months or more from the end of (neo-)adjuvant therapy Previous radiotherapy, either in the adjuvant setting or for the treatment of bone metastases, is allowed provided that the measurable lesions are outside the radiation fields Persistence of clinically relevant treatment-related toxicities from previous chemotherapy and/or radiotherapy (adjuvant or neo-adjuvant setting) Treatment with other investigational drugs or treatment in another clinical trial within the past four weeks before start of treatment or concomitantly with this trial Known alcohol or drug abuse Clinically significant cardiovascular disease Evidence of uncontrolled medical comorbidities despite adequate treatment Patients who have suffered a cerebrovascular accident or transient ischemic attack within the past 12 months History, within the past 5 years, of malignancies other than CRC Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and followup schedule
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Peeters, MD, PhD
Organizational Affiliation
UNIVERSITAIR ZIEKENHUIS ANTWERPEN, Edegem, Belgium
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ulrich Wedding, MD
Organizational Affiliation
UNIVERSITAETSKLINIKUM JENA, Jena, Germany
Official's Role
Study Chair
Facility Information:
Facility Name
AZ Turnhout - Campus Sint Elisabeth
City
Turnhout
Country
Belgium
Facility Name
Bank Of Cyprus Oncology Centre
City
Nicosia
Country
Cyprus
Facility Name
Hospital General Vall D'Hebron
City
Barcelona
Country
Spain

12. IPD Sharing Statement

Links:
URL
http://www.eortc.be/clinicaltrials/details.asp?protocol=40085
Description
Related Info

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Colorectal Cancer (CRC) Cetuximab Elderly Frail

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