Colorectal Cancer (CRC) Cetuximab Elderly Frail

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01522612
First received: January 27, 2012
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: Cetuximab
Drug: 5-fluorouracil
Drug: leucovorin
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: 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).

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: No ]
    Progression will be defined according to the "RECIST V1.1"


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: No ]
  • Response Rate [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: No ]
    according to the RECIST V1.1

  • Change in Instrumental Activities of Daily Living (IADL) score [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: No ]
  • Change in G8 geriatric assessment screening tool [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: No ]
  • Change in social situation [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Occurrence of adverse events [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: Yes ]
    Adverse events will be graded according to the "Common Terminology Criteria for Adverse events" CTCAE,version 4.0.

  • Health Economy assessments [ Time Frame: 19 months from first patient in ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: April 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5-fluorouracil/leucovorin plus cetuximab Drug: Cetuximab
500 mg/m2 on day 1, Every 14 days Intravenously
Other Name: Erbitux
Drug: 5-fluorouracil
Every 2 weeks, 400 mg/m2 on day 1; 2400 mg/m2 from day 1 to day 3, intravenously
Other Name: 5-FU
Drug: leucovorin
Every 2 weeks, Racemic leucovorin 200 mg/m2 or l-leucovorin 100 mg/m2 on day 1, intravenously
Other Name: 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 Name: 5-FU
Drug: leucovorin
Every 2 weeks, Racemic leucovorin 200 mg/m2 or l-leucovorin 100 mg/m2 on day 1, intravenously
Other Name: Folinic Acid

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.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01522612

Contacts
Contact: Nicolas Dif, PhD +32 2 774 10 43 nicolas.dif@eortc.be
Contact: Carlo G. Messina, MD M.Phil +32 2 774 15 18 carlo.messina@eortc.be

Locations
Belgium
ZNA Middelheim Recruiting
Antwerpen, Belgium
Principal Investigator: Franck Van Fraeyenhove         
Hopital Universitaire Brugmann Recruiting
Brussels, Belgium
Principal Investigator: André Efira         
Cliniques Universitaires Saint-Luc Recruiting
Brussels, Belgium
Principal Investigator: Marc Van den Eynde         
Universitair Ziekenhuis Antwerpen Recruiting
Edegem, Belgium
Principal Investigator: Marc Peeters         
Universitair Ziekenhuis Gent Recruiting
Gent, Belgium
Principal Investigator: Karen Geboes         
Hopital De Jolimont Recruiting
Haine St Paul, Belgium
Principal Investigator: Bénédicte Petit         
C.H.U. Sart-Tilman Recruiting
Liege, Belgium
Principal Investigator: Marc Polus         
AZ Damiaan Recruiting
Oostende, Belgium
Principal Investigator: Guy Deboever         
AZ Turnhout - Campus Sint Elisabeth Recruiting
Turnhout, Belgium
Principal Investigator: Jozef Janssens         
Centre Hospitalier Peltzer-La Tourelle Recruiting
Verviers, Belgium
Principal Investigator: Hassan Rezaei Kalantari         
Cyprus
Bank Of Cyprus Oncology Centre Recruiting
Nicosia, Cyprus
Principal Investigator: Demetris Papamichael         
Italy
Seconda Universita Degli Studi Di Napoli Recruiting
Napoli, Italy
Principal Investigator: Fortunato Ciardiello         
Spain
Hospital General Vall D'Hebron Recruiting
Barcelona, Spain
Principal Investigator: Elena Elez         
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Merck KGaA
Investigators
Study Chair: Marc Peeters, MD, PhD UNIVERSITAIR ZIEKENHUIS ANTWERPEN, Edegem, Belgium
Study Chair: Ulrich Wedding, MD UNIVERSITAETSKLINIKUM JENA, Jena, Germany
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01522612     History of Changes
Other Study ID Numbers: EORTC-40085-75083, 2011-002947-83
Study First Received: January 27, 2012
Last Updated: January 20, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
KRAS Wild Type
Frail Elderly
QLQ-C30
QLQ-ELD14
CGA
EGFR
Cetuximab
5-FU

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

ClinicalTrials.gov processed this record on October 19, 2014