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

Quality of Life Clinical Trial

— COLAGE  

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03828227
• Other study ID #: COLAGE C18-01 PRODIGE 66
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 14, 2019
• Est. completion date: September 30, 2024

Study information

• Verified date: January 2024
• Source: GERCOR - Multidisciplinary Oncology Cooperative Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: September 30, 2024
• Est. primary completion date: November 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Elderly Patients
• Metastatic Colorectal Cancer
• Quality of Life

Intervention

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
• 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).

Locations

Country	Name	City	State
France	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	Saint-Malo

Sponsors (1)

Lead Sponsor	Collaborator
GERCOR - Multidisciplinary Oncology Cooperative Group

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of patients amenable to second-line therapy.	Proportion of patients amenable to second-line therapy.	until 58 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Performance status geriatric (PSG) score.	External analysis of PSG score as predictive for treatment efficacy: PFS and OS.	until 58 months