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

Study Overview
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Brief Summary
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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
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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

Official Title
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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.

Conditions
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Metastatic Colorectal Cancer, Quality of Life, Elderly Patients

Intervention / Treatment
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* Drug: OPTIMOX-bevacizumab
* Drug: Capecitabine plus bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent, and willing and able to comply with protocol requirements, Histologically proven colorectal adenocarcinoma, Confirmed metastatic disease, Patients with no detected dihydropyridine dehydrogenase (DPD) deficiency, 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, Duly documented unresectable metastatic disease i.e., not suitable for complete carcinological surgical resection, Age ≥ 75 years, ECOG PS 0-2, Hematological status: neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, and hemoglobin > 9 g/dL, Adequate renal function: serum creatinine level < 150 µmol/l, and creatinine clearance (Cockcroft and Gault or MDRD formula > 30 mL/min), Adequate liver function: total bilirubin level < 1.5 x upper normal limit (ULN), serum alkaline phosphatase (ALP) level < 5 x ULN, Proteinuria < 2+ (dipstick urinalysis) or ≤ 1g/24h, Regular follow-up feasible. The registered patient must be treated and followed at the participating center, Registration in France with the French National Health Care System (including dispositive PUMA (protection Universelle Maladie). Exclusion Criteria: 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, Neuropathy grade > 1, 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 Uncontrolled hypercalcemia, Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy, 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, History of arterial thrombotic and/or embolic event (e.g. myocardial infarction, stroke…) within 6 months prior to randomization, History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to randomization, History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding, 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, Concomitant administration of prophylactic phenytoin, Treatment with sorivudine or its chemically related analogues, such as brivudine, Patients with known allergy/hypersensitivity to any component of study drugs Concomitant unplanned anti-tumor treatment, Participation in another clinical trial with any investigational drug within 30 days prior to randomization, Other serious and uncontrolled non-malignant disease, Patient under guardianship, curatorship or under the protection of justice

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Candidate group OPTIMOX plus bevacizumab (Arm A)<br>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<br>* 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<br>* Other names: Avastin;|
| Active Comparator: Candidate group - Capecitabine-bevacizumab (Arm B)<br>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<br>* 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).<br>* Other names: Avastin;|
| Active Comparator: Non candidate group - Capecitabine-bevacizumab<br>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<br>* 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).<br>* Other names: Avastin;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemotherapy