Colorectal Cancer (CRC) Cetuximab Elderly Frail

June 9, 2016 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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).

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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:

  1. Total number of randomized patients: 150.
  2. Total number of events at phase II analysis for primary endpoint: 110.
  3. Total number of patients screened over the phase II: 250.
  4. Total number of patients treated with cetuximab for the Phase II study: 75.
  5. 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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Turnhout, Belgium
        • AZ Turnhout - Campus Sint Elisabeth
  • Cyprus
      • Nicosia, Cyprus
        • Bank Of Cyprus Oncology Centre
  • Spain
      • Barcelona, Spain
        • Hospital General Vall D'Hebron

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

70 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 5-fluorouracil/leucovorin plus cetuximab
Drug: Cetuximab
500 mg/m2 on day 1, Every 14 days Intravenously
Other Names:
  • Erbitux
Drug: 5-fluorouracil
Every 2 weeks, 400 mg/m2 on day 1; 2400 mg/m2 from day 1 to day 3, intravenously
Other Names:
  • 5-FU
Drug: leucovorin
Every 2 weeks, Racemic leucovorin 200 mg/m2 or l-leucovorin 100 mg/m2 on day 1, intravenously
Other Names:
  • Folinic Acid
Active Comparator: 5-fluorouracil/leucovorin alone
Drug: 5-fluorouracil
Every 2 weeks, 400 mg/m2 on day 1; 2400 mg/m2 from day 1 to day 3, intravenously
Other Names:
  • 5-FU
Drug: leucovorin
Every 2 weeks, Racemic leucovorin 200 mg/m2 or l-leucovorin 100 mg/m2 on day 1, intravenously
Other Names:
  • Folinic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 19 months from first patient in
Progression will be defined according to the "RECIST V1.1"
19 months from first patient in

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 19 months from first patient in
19 months from first patient in
Response Rate
Time Frame: 19 months from first patient in
according to the RECIST V1.1
19 months from first patient in
Change in Instrumental Activities of Daily Living (IADL) score
Time Frame: 19 months from first patient in
19 months from first patient in
Change in G8 geriatric assessment screening tool
Time Frame: 19 months from first patient in
19 months from first patient in
Change in social situation
Time Frame: 19 months from first patient in
19 months from first patient in
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
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Occurrence of adverse events
Time Frame: 19 months from first patient in
Adverse events will be graded according to the "Common Terminology Criteria for Adverse events" CTCAE,version 4.0.
19 months from first patient in
Health Economy assessments
Time Frame: 19 months from first patient in
19 months from first patient in
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
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
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
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
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
14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Chair: Marc Peeters, MD, PhD, UNIVERSITAIR ZIEKENHUIS ANTWERPEN, Edegem, Belgium
  • Study Chair: Ulrich Wedding, MD, UNIVERSITAETSKLINIKUM JENA, Jena, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

January 27, 2012

First Submitted That Met QC Criteria

January 30, 2012

First Posted (Estimate)

January 31, 2012

Study Record Updates

Last Update Posted (Estimate)

June 10, 2016

Last Update Submitted That Met QC Criteria

June 9, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-40085-75083
  • 2011-002947-83 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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