QoL in mCRC Elderly Patients Receiving First-line Therapy Based on Simplified Geriatric Parameters. (COLAGE)

Phase III Study to Evaluate the Quality of Life in Elderly Patients With Metastatic Colorectal Cancer Receiving First-line Therapy Based on Simplified Geriatric Parameters.

A national, multicenter, open-label, randomized phase III study. The trial aim is to determine the best therapeutic strategies according with the HRQoL.

Study Overview

• Status: Active, not recruiting
• Conditions: Quality of Life; Metastatic Colorectal Cancer; Elderly Patients
• Intervention / Treatment: Drug: Capecitabine plus bevacizumab; Drug: OPTIMOX-bevacizumab

Detailed Description

Treatment cohort will be determined based on three parameters:

• Serum albumin level at baseline,
• ECOG Performance Status,
• Mini GDS.

The "Candidate" group will be defined according to (all the following criteria must be fulfilled):

• Serum albumin level ≥ 30g/L,
• ECOG PS 0-1 (whatever mini GDS score) or ECOG PS 2 with mini GDS 0 (ie, no depression).

The "Non-candidate" cohort group will be defined according to (at least one of those parameters is fulfilled):

• Serum albumin level < 30g/L.
• And/ or ECOG PS 2 and mini GDS ≥ 1 (ie, depression).

Patients in the "Candidate group" will be randomized to:

• OPTIMOX bevacizumab (arm A),
• Capecitabine + bevacizumab (arm B), in priority followed by FOLFOX-bevacizumab at first progression.

Patients in the "Non-candidate" group cohort

- Not randomized, follow-up patients receiving: capecitabine + bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Abbeville, France
    • CH Abbeville
  • Amiens, France
    • Clinique de l'Europe
  • Amiens, France
    • CHU Amiens Hopital Sud
  • Beauvais, France
    • CH Beauvais
  • Boulogne-sur-Mer, France
    • Hopital Duchenne
  • Cannes, France
    • Centre Hospitalier de Cannes
  • Compiègne, France
    • CH Compiègne Noyon
  • Creil, France
    • UCOG Picardie Groupe Hospitalier
  • Créteil, France
    • CHU Henri Mondor
  • Dijon, France
    • Centre geroges François Leclerc
  • Grenoble, France
    • Institut Daniel Hollard
  • Levallois-Perret, France
    • Institut Hospitalier Franco-Britannique
  • Lyon, France
    • Hôpital privé Jean Mermoz
  • Marseille, France
    • Institut Paoli-Calmettes
  • Melun, France
    • CH Sud Ile de France
  • Mont-de-Marsan, France
    • CH Mont de Marsan
  • Nice, France
    • Centre Antoine Lacassagne
  • Paris, France
    • Institut Mutualiste Montsouris
  • Paris, France
    • Hopital Saint Antoine
  • Paris, France
    • Hôpital des Diaconnesses Croix Saint Simon
  • Pringy, France
    • CH Annecy Genevois
  • Saint-Malo, France
    • CH Saint Malo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. Histologically proven colorectal adenocarcinoma,
3. Confirmed metastatic disease,
4. Patients with no detected dihydropyridine dehydrogenase (DPD) deficiency,
5. No prior therapy for metastatic disease (in case of previous adjuvant chemotherapy, interval between the end of chemotherapy and relapse must be > 6 months for fluoropyrimidine alone or > 12 months for oxaliplatin-based chemotherapy,
6. Duly documented unresectable metastatic disease i.e., not suitable for complete carcinological surgical resection,
7. Age ≥ 75 years,
8. ECOG PS 0-2,
9. Hematological status: neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, and hemoglobin > 9 g/dL,
10. Adequate renal function: serum creatinine level < 150 µmol/l, and creatinine clearance (Cockcroft and Gault or MDRD formula > 30 mL/min),
11. Adequate liver function: total bilirubin level < 1.5 x upper normal limit (ULN), serum alkaline phosphatase (ALP) level < 5 x ULN,
12. Proteinuria < 2+ (dipstick urinalysis) or ≤ 1g/24h,
13. Regular follow-up feasible. The registered patient must be treated and followed at the participating center,
14. Registration in France with the French National Health Care System (including dispositive PUMA (protection Universelle Maladie).

Exclusion Criteria:

1. History or evidence upon physical examination of CNS metastasis (e.g. non- irradiated CNS metastasis, seizure not controlled with standard medical therapy), unless adequately treated,
2. Neuropathy grade > 1,
3. Patient with known dihydropyridine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to a fluoropyrimidine-containing regimen, or in case of clinically significant active heart disease or myocardial infarction within 6 months or if patient treated with sorivudine or its clinically related analogues, such as brivudine
4. Uncontrolled hypercalcemia,
5. Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy,
6. Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥ 5 years,
7. History of arterial thrombotic and/or embolic event (e.g. myocardial infarction, stroke…) within 6 months prior to randomization,
8. History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to randomization,
9. History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding,
10. Major surgery (open biopsy, surgical resection, wound revision or any other major surgery involving entry into body cavity) or significant traumatic injury within the last 28 days prior to randomization, and/or minor surgical procedure including placement of a vascular device within 2 days of first study treatment,
11. Concomitant administration of prophylactic phenytoin,
12. Treatment with sorivudine or its chemically related analogues, such as brivudine,
13. Patients with known allergy/hypersensitivity to any component of study drugs
14. Concomitant unplanned anti-tumor treatment,
15. Participation in another clinical trial with any investigational drug within 30 days prior to randomization,
16. Other serious and uncontrolled non-malignant disease,
17. Patient under guardianship, curatorship or under the protection of justice

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: "Candidate group" OPTIMOX plus bevacizumab (Arm A); Patients with : Serum albumin level ≥ 30g/L,; ECOG PS 0-1 (whatever mini GDS score) or ECOG PS 2 with mini GDS 0 (ie, no depression). Adapted FOLFOX7 (aFOLFOX7)-bevacizumab for 6 cycles and then Adapted LV5FU2 (aLV5FU2)-bevacizumab (until progression or or unacceptable limiting toxicity)	Drug: OPTIMOX-bevacizumab; Induction Adapted FOLFOX7 (aFOLFOX7)-bevacizumab for 6 cycles (3 months); Bevacizumab: 5 mg/kg IV (day 1, every 2 weeks [q2w]),; Folinic acid (FA): 400 mg/m² IV/2h (day 1, q2w),; Oxaliplatin: 85 mg/m² IV/2h (day 1, q2w),; 5-fluorouracil (5-FU) continuous infusion 2400 mg/m² IV/46h (day 1-2, q2w),; No 5-FU bolus. then Maintenance Adapted LV5FU2 (aLV5FU2)-bevacizumab (until progression or or unacceptable limiting toxicity); Bevacizumab: 5 mg/kg IV (day 1, q2w),; FA: 400 mg/m² IV/2h (day 1, q2w),; 5-FU continuous infusion 2400 mg/m² IV/46h (day 1-2, q2w); No 5-FU bolus; Other Names: Avastin; Folinic acid (FA)-5-fluorouracil (5-FU)-oxaliplatin [OPTIMOX]
Active Comparator: "Candidate group" - Capecitabine-bevacizumab (Arm B); Patients with : Serum albumin level ≥ 30g/L,; ECOG PS 0-1 (whatever mini GDS score) or ECOG PS 2 with mini GDS 0 (ie, no depression). This treatment regimen will be given until disease progression (PD) or unacceptable limiting toxicity, as follows:	Drug: Capecitabine plus bevacizumab; Bevacizumab: 7.5 mg/kg intravenous infusion [IV] (day 1; q3w),; Capecitabine: 1000 mg/m² orally twice a day (day 1 through day 14, q3w).; Other Names: Avastin; capecitabine
Active Comparator: "Non candidate group" - Capecitabine-bevacizumab; Patients with: Serum albumin level < 30g/L.; And/ or ECOG PS 2 and mini GDS ≥ 1 (ie, depression). This treatment regimen will be given until disease progression (PD) or unacceptable limiting toxicity, as follows:	Drug: Capecitabine plus bevacizumab; Bevacizumab: 7.5 mg/kg intravenous infusion [IV] (day 1; q3w),; Capecitabine: 1000 mg/m² orally twice a day (day 1 through day 14, q3w).; Other Names: Avastin; capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life (HRQoL) at 6 months in the "candidate group".	Improvement of HRQoL at 6 months by 10 points compared to the score at inclusion on the following targeted dimensions: emotional functioning (4 items) and global health (2 items) (score from 6-30 with higher values representing better quality of life).	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients amenable to second-line therapy.	Proportion of patients amenable to second-line therapy.	until 58 months
Number of patient amenable to surgery and/or locoregional therapy.	Proportion of patients amenable to salvage surgery and/or locoregional therapy (e.g., radiofrequency ablation, stereotactic radiotherapy, …).	until 58 months
Progression-free survival (PFS)	PFS is defined as time from date of first dose of study treatment to date of first documented PD or death due to any cause determined by the Investigator assessment in accordance to RECIST 1.1. Alive patients without progression will be censored at the last tumor assessment, either during study treatment period or during follow-up period.	until 58 months
Overall survival (OS)	OS defined as the time between the date of the first dose of study treatment and the death date. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period.	Until 58 months
Other dimensions of health-related quality of life (HRQoL) and longitudinal HRQoL	HRQoL: all other dimensions of the QLQC-30 and QLQELD-14 questionnaires, and longitudinal analyses of the QLQC-30 and QLQELD-14 elderly specific module integrating all measurement times.	Until 58 months
Determination of instrumental activities of daily living (IADL) as prognostic factor for overall survival (OS).	IADL as prognostic factor for overall survival (OS) and treatment toxicity.	Until 58 months
G8 score at baseline.	To determine G8 score at baseline and to correlate the candidate group and the non-candidate group according to G8 score.	until 58 months
Performance status geriatric (PSG) score.	External analysis of PSG score as predictive for treatment efficacy: PFS and OS.	until 58 months

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Principal Investigator: Elisabeth CAROLA, MD, UCOG Picardie Groupe Hospitalier Public du Sud de l'Oise (GHPSO)

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2019
• Primary Completion (Actual): November 10, 2023
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 29, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab; Fluorouracil
• Other Study ID Numbers: COLAGE C18-01 PRODIGE 66

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No