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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).

Phase 2
70 Years
Open (Enrolling)
Colorectal Cancer Metastatic

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Trial Information

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).

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

- 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:

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.

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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival

Outcome Description:

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

Outcome Time Frame:

19 months from first patient in

Safety Issue:


Principal Investigator

Marc Peeters, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:



Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:




Start Date:

April 2013

Completion Date:

September 2015

Related Keywords:

  • Colorectal Cancer Metastatic
  • KRAS Wild Type
  • Frail Elderly
  • QLQ-C30
  • QLQ-ELD15
  • CGA
  • EGFR
  • Cetuximab
  • 5-FU
  • Colorectal Neoplasms
  • Neoplasms
  • Neoplasms, Second Primary