Randomised Study Evaluating Adjuvant Chemotherapy After Resection of Stage III Colonic Adenocarcinoma in Patients of 70 and Over

Phase 3

Recruiting

• Conditions: Colonic Adenocarcinoma
• Interventions: Drug: LV5FU2 or capecitabine; Drug: LV5FU2 or capectitabine; Drug: FOLFOX4 or XELOX; Other: Observation

• Registration Number: NCT02355379
• Lead Sponsor: Federation Francophone de Cancerologie Digestive

Brief Summary

Colorectal cancer occurs mainly in elderly patients. Recent estimation showed that in France more than 50% of the patients diagnosed with a colorectal cancer are 70 years old or more. Adjuvant chemotherapy has demonstrated a benefit on disease-free survival and overall survival after a stage III colon cancer resection. Nevertheless adjuvant chemotherapy is poorly used in elderly patients. Prognostic improvement with chemotherapy based on 5FU is suggested by a post-hoc analysis of randomized prospective clinical trial. But elderly patients in this study were highly selected and patients older than 80 represented only 0.7% of the total population. Thus, there is still a concern about the benefit of adjuvant 5FU-based chemotherapy in very elderly unselected patients.

The recommended treatment for stage III adjuvant chemotherapy is a combination of fuoropyrimidine and oxaliplatin. Nevertheless oxaliplatin did not demonstrated survival advantage in elderly patients.

Altogether there are still two matters of debate:

* First, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for unfit elderly patients?

* Second, is there a benefit of oxaliplatin-based adjuvant chemotherapy for fit elderly patients? The aim of this randomized phase III study is to evaluate the benefit for disease-free survival of adjuvant chemotherapy in elderly patient and which chemotherapy.

The elderly patient population will be dichotomized into two groups according to physician's choice after a multidisciplinary evaluation involving a geriatrician, with two different randomization assignments. The patients with an expected life-expectancy below 4 years according Lee score are excluded of this study.

Some biological tumour abnormalities are more frequently observed in elderly (i.e. mismatch repair deficiency), therefore an evaluation of specific biological prognostic factors is needed in elderly population.

Detailed Description

Colorectal cancer occurs mainly in elderly patients. Recent estimation showed that in France more than 50% of the patients diagnosed with a colorectal cancer are 70 years old or more. Adjuvant chemotherapy has demonstrated a benefit on disease-free survival and overall survival after a stage III colon cancer resection. Nevertheless adjuvant chemotherapy is poorly used in elderly patients. Prognostic improvement with chemotherapy based on 5FU is suggested by a post-hoc analysis of randomized prospective clinical trial. But elderly patients in this study were highly selected and patients older than 80 represented only 0.7% of the total population. Thus, there is still a concern about the benefit of adjuvant 5FU-based chemotherapy in very elderly unselected patients.

The recommended treatment for stage III adjuvant chemotherapy is a combination of fuoropyrimidine and oxaliplatin. Nevertheless oxaliplatin did not demonstrated survival advantage in elderly patients.

Altogether there are still two matters of debate:

* First, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for unfit elderly patients?

* Second, is there a benefit of oxaliplatin-based adjuvant chemotherapy for fit elderly patients? The aim of this randomized phase III study is to evaluate the benefit for disease-free survival of adjuvant chemotherapy in elderly patient and which chemotherapy.

The elderly patient population will be dichotomized into two groups according to physician's choice after a multidisciplinary evaluation involving a geriatrician, with two different randomization assignments. The patients with an expected life-expectancy below 4 years according Lee score are excluded of this study.

Some biological tumour abnormalities are more frequently observed in elderly (i.e. mismatch repair deficiency), therefore an evaluation of specific biological prognostic factors is needed in elderly population.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-01-26
• Study First Submitted QC: 2015-02-03
• Study First Posted: 2015-02-04
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-05
• Last Update Posted: 2024-07-08
• Primary Completion: 2024-12
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 774

Inclusion Criteria

• Age ≥ 70 years
• Patient considered able to receive chemotherapy
• Lee score detailed faxed to CRGA
• Stage III colon adenocarcinoma
• R0 resection of the primary tumor
• Start of the potential adjuvant chemotherapy within 12 weeks after surgery
• No prior chemotherapy for colon cancer
• Geriatric Self-administered questionnaire completed faxed to CRGA
• Geriatric Questionnaire completed by the team faxed to CRGA
• Effective contraception for men patients throughout treatment and for at least 6 months after discontinuation of oxaliplatin
• Consent signed

Exclusion Criteria

• Other progressive disease (cancer uncontrolled for less than 2 years)
• Rectal Cancer (located less than 15 cm from the anal verge endoscopy or sub-peritoneal)
• ANC <2000 / mm3 for group 1 and ANC <1500 / mm3 for group 2 and platelets <100,000 / mm3 or hemoglobin <9 g / dL
• Neuropathy for patients in group 1
• Known deficit of dihydropyrimidine dehydrogenase (DPD)
• Patients with severe hepatic insufficiency
• Any contrindication to the drugs used in the study
• Inability to submit to medical follow-up for geographical, social or psychological reasons.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GROUP2-ARM D	LV5FU2 or capecitabine	LV5FU2 or capecitabine
GROUP1 -ARM A	LV5FU2 or capectitabine	LV5FU2 or capecitabine
GROUP1-ARMB	FOLFOX4 or XELOX	FOLFOX4 or XELOX
GROUP2- ARM C	Observation	Observation

Primary Outcome Measures

Name	Time	Method
The 3-year disease-free survival	3 years after last patient in

Secondary Outcome Measures

Name	Time	Method
Overal survival	5 years after last patient in
Observed toxicities, graded according to NCI-CTC v4	3 years after last patient in

Trial Locations

Locations (119)

CHU de Fort de France; 🇫🇷 Fort De France, Guadeloupe, France

CH d'Abbeville; 🇫🇷 Abbeville CEDEX, France

CROMG; 🇫🇷 Agen, France

Centre hospitalier du Pays d'Aix; 🇫🇷 Aix-en-Provence, France

Centre hospitalier d'Albi; 🇫🇷 Albi, France

Clinique Claude Bernard; 🇫🇷 Albi, France

Centre Oncogard; 🇫🇷 Nîmes CEDEX 9, France

Hôpital Sud; 🇫🇷 Amiens CEDEX 1, France

ICO Site Paul Papin; 🇫🇷 Angers CEDEX 2, France

CHU d'Angers; 🇫🇷 Angers CEDEX 9, France

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