Colorectal Cancer (CRC) Cetuximab Elderly Frail
This study is currently recruiting participants.
Verified May 2013 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
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: May 30, 2013
Last verified: May 2013
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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-ELD15) [ 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-ELD15 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.
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: absolute neutrophil count ≥1.5 x 109 cells/L, platelets ≥100 x 109 cells/L and uncorrected hemoglobin ≥10 g/dL (i.e., without blood transfusion or use of erythropoietin)
- Adequate hepatic function: either AST or ALT ≤ 2.5x ULN (in presence of liver metastases, either AST or ALT ≤ 5x ULN), total bilirubin <1.5xULN
- Adequate renal function: GFR > 60 ml/min as measured by Modification of Diet in Renal Disease formula before receiving chemotherapy
- Normal 12 lead ECG without clinically significant abnormalities
- Sexually active male participants must use barrier methods of contraception. Contraception period: from the treatment start, throughout the study, and until 30 days after the last protocol treatment administration.
- 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 (uncontrolled hypertension, New York Heart Association class II-IV congestive heart failure, unstable angina pectoris within the past 12 months, peripheral vascular disease ≥ grade 2, serious cardiac arrhythmia requiring medication, myocardial infarction within the past 12 months, other clinically significant cardiovascular disease)
- Evidence of uncontrolled medical comorbidities despite adequate treatment (according to treating physician) like Diabetes mellitus, Chronic Obstructive Pulmonary Disease (COPD), Serious infections requiring systemic antibiotic therapy (e.g. antimicrobial, antifungal, antiviral)
- 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 (except: adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, resected incidental prostate cancer staged pT2 with Gleason Score <= 6 and postoperative PSA < 0.5 ng/ml). Patients with any history of malignancies who are disease-free for more than 5 years are eligible
- Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and followup schedule, those conditions should be discussed with the patient before registration in the trial
Contacts and Locations
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 | |
| Universitair Ziekenhuis Antwerpen | Recruiting |
| Edegem, Belgium | |
| AZ Turnhout - Campus Sint Elisabeth | Recruiting |
| Turnhout, Belgium | |
| Centre Hospitalier Peltzer-La Tourelle | Recruiting |
| Verviers, Belgium | |
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: | May 30, 2013 |
| 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-ELD15 |
CGA EGFR Cetuximab 5-FU |
Additional relevant MeSH terms:
|
Colorectal Neoplasms Neoplasms Neoplasms, Second Primary Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Fluorouracil Cetuximab Leucovorin |
Levoleucovorin Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Vitamin B Complex Vitamins Micronutrients Growth Substances Antidotes |
ClinicalTrials.gov processed this record on June 18, 2013