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

NCT ID: NCT03828227

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-14
• Study Completion Date: 2025-12-31

Brief Summary

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

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

Conditions

Elderly Patients; Metastatic Colorectal Cancer; Quality of Life

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

"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)

Group Type: ACTIVE_COMPARATOR

OPTIMOX-bevacizumab

Intervention Type: DRUG

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

"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:

Group Type: ACTIVE_COMPARATOR

Capecitabine plus bevacizumab

Intervention Type: DRUG

• 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).

"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:

Group Type: ACTIVE_COMPARATOR

Capecitabine plus bevacizumab

Intervention Type: DRUG

• 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).

Interventions

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

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Folinic acid (FA)-5-fluorouracil (5-FU)-oxaliplatin [OPTIMOX]; Avastin; capecitabine; Avastin

Eligibility Criteria

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

• Minimum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GERCOR - Multidisciplinary Oncology Cooperative Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elisabeth CAROLA, MD

Role: PRINCIPAL_INVESTIGATOR

UCOG Picardie Groupe Hospitalier Public du Sud de l'Oise (GHPSO)

Locations

CH Abbeville

Abbeville, , France

CHU Amiens Hôpital sud

Amiens, , France

Clinique de l'Europe

Amiens, , France

CH Beauvais

Beauvais, , France

Hôpital Duchenne

Boulogne-sur-Mer, , France

Centre hospitalier de Cannes

Cannes, , France

CH Compiègne Noyon

Compiègne, , France

UCOG Picardie Groupe Hospitalier

Creil, , France

CHU Henri Mondor

Créteil, , France

Centre geroges François Leclerc

Dijon, , France

Institut Daniel Hollard

Grenoble, , France

Institut Hospitalier Franco-Britannique

Levallois-Perret, , France

Hôpital Privé Jean Mermoz

Lyon, , France

Institut Paoli-Calmettes

Marseille, , France

CH Sud Ile de France

Melun, , France

CH Mont de Marsan

Mont-de-Marsan, , France

Centre Antoine Lacassagne

Nice, , France

Hôpital des Diaconnesses Croix Saint Simon

Paris, , France

Hôpital Saint Antoine

Paris, , France

Institut Mutualiste Montsouris

Paris, , France

CH Annecy Genevois

Pringy, , France

CH Saint Malo

St-Malo, , France

Countries

France

Other Identifiers

COLAGE C18-01 PRODIGE 66

Identifier Type: -

Identifier Source: org_study_id