Clinical trial NCT03828227: QoL in mCRC Elderly Patients Receiving First-line Therapy Based on Simplified Geriatric Parameters.
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Elderly Patients
Metastatic Colorectal Cancer
Quality of Life
Keywords: chemotherapy
Lead sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
Sponsor class: OTHER
First posted: 2019-02-04
Enrollment: 49
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

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

Primary outcomes:
measure: Health-related quality of life (HRQoL) at 6 months in the "candidate group".
timeFrame: At 6 months
Secondary outcomes:
measure: Number of patients amenable to second-line therapy.
timeFrame: until 58 months
measure: Number of patient amenable to surgery and/or locoregional therapy.
timeFrame: until 58 months
measure: Progression-free survival (PFS)
timeFrame: until 58 months
measure: Overall survival (OS)
timeFrame: Until 58 months
measure: Other dimensions of health-related quality of life (HRQoL) and longitudinal HRQoL
timeFrame: Until 58 months
measure: Determination of instrumental activities of daily living (IADL) as prognostic factor for overall survival (OS).
timeFrame: Until 58 months
measure: G8 score at baseline.
timeFrame: until 58 months
measure: Performance status geriatric (PSG) score.
timeFrame: until 58 months
Other outcomes:
Locations:
city: Abbeville
country: France
facility: CH Abbeville
city: Amiens
country: France
facility: CHU Amiens Hôpital sud
city: Amiens
country: France
facility: Clinique de l'Europe
city: Beauvais
country: France
facility: CH Beauvais
city: Boulogne-sur-Mer
country: France
facility: Hôpital Duchenne
city: Cannes
country: France
facility: Centre hospitalier de Cannes
city: Compiègne
country: France
facility: CH Compiègne Noyon
city: Creil
country: France
facility: UCOG Picardie Groupe Hospitalier
city: Créteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: Centre geroges François Leclerc
city: Grenoble
country: France
facility: Institut Daniel Hollard
city: Levallois-Perret
country: France
facility: Institut Hospitalier Franco-Britannique
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Melun
country: France
facility: CH Sud Ile de France
city: Mont-de-Marsan
country: France
facility: CH Mont de Marsan
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hôpital des Diaconnesses Croix Saint Simon
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Pringy
country: France
facility: CH Annecy Genevois
city: Saint-Malo
country: France
facility: CH Saint Malo
Study officials:
affiliation: UCOG Picardie Groupe Hospitalier Public du Sud de l'Oise (GHPSO)
name: Elisabeth CAROLA, MD
role: PRINCIPAL_INVESTIGATOR
References: