ATTENUATION – A multicenter randomized phase II study of the efficacy and safety de-escalation versus standard adjuvant chemotherapy in patients with low risk localized gastroesophageal adenocarcinoma (study PRODIGE/FRENCH 39)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Leon Berard

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

completed 2 Jun 2026

Decision date (initial)

2024-07-23

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCA/DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Evaluate the efficacy (3-year OS rate) of a de-escalation strategy (surveillance) compared to the standard post-operative chemotherapy schedule in patients with low-risk of relapse, previously treated with pre-operative chemotherapy (4 cycles of FLOT) and complete resection of a gastric, junctional or esophageal adenocarcinoma.

The co-primary objective is to evaluate the 3-year Disease-Free Survival rate of the surveillance arm compared to the standard arm.

Secondary objectives 5

1. • Overall survival (OS)
2. • Disease-Free Survival (DFS)
3. • Pattern and rate of relapse
4. • Tolerability profile
5. • Health-related quality of life and nutritional status, and correlation of these parameters with survival outcomes

Conditions and MedDRA coding

Low risk of disease recurrence, defined by the following criteria: - Absence of lymph node involvement (ypN0), assessed on a min. of 15 lymph nodes and, - Either ypT0-2 ( all TRG grade) or ypT3 (with TRG 1a-b according to Becker classification or TRG1-2 according to Mandard’s classification),

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. I1. Age ≥ 18 years
2. I2. Histologically proven non-metastatic (M0) gastric, esophageal or gastroesophageal junction adenocarcinoma
3. I3. Subjects must have completed both pre-operative chemotherapy with a fluoropyrimidine-platinum containing regimen (FLOT 4 cycles) and microscopically complete (R0) resection prior to randomization. Note for surgery: total or distal gastrectomy with D2 lymphadenectomy according to ESMO guidelines should have been completed for gastric and junctional Siewert type III cancers. Ivor Lewis oesophagectomy with two field lymphadenectomy should have been performed for junctional Siewert type I cancers and lower esophageal adenocarcinomas. For Siewert type II cancers either total gastrectomy with D2-lymphadenectomy or oesophagectomy with two field lymphadenectomy should have been completed. Open, minimal invasive or hybrid surgical approaches are acceptable as long as the requirements above are fulfilled. In frail patients with Siewert I or II, transhiatal oesophagectomy with lymphadenectomy in the lower mediastinum without transthoracic access is acceptable. Regardless of the type of surgery a minimum of 16 (gastric cancer) or 7 lymph nodes (in case of esophageal carcinoma) should have been resected and examined (ref TNM 8 eme edition
4. I4. Low risk of disease recurrence, defined by the following criteria: - Absence of lymph node involvement (ypN0), assessed on a min. of 16 or 7 lymph nodes according to the localization and, - Either ypT0-2 (all TRG grade) or ypT3 (with TRG 1a-b according to Becker classification or TRG1-2 according to Mandard’s classification),
5. I5. ECOG Performance Status 0-1
6. I6. Patients fit to receive post-operative chemotherapy
7. I7. Interval between the date of surgery and the date of randomization no longer than 10 weeks
8. I8. Adequate organs function (ranges defined in the clinical trial protocol)
9. I9. No contraindication to study assessments,
10. I10. Signed and dated informed consent for prior to any study-specific procedure
11. I11. Women of childbearing potential accepting to use highly effective contraceptive measures or abstain from heterosexual activity, for the course of the study and at least an- 9 months after the end of the treatment with oxaliplatin - 6 months after the end of the treatment with fluorouracil - 2 months after the end of the treatment with docetaxel and men must use contraception during treatment and at least - 6 months after the end of the treatment with oxaliplatin, - 3 months after the end of the treatment with fluorouracil - 4 months after the end of the treatment with docetaxel.
12. I12. Patient must be covered by a medical insurance or equivalent

Exclusion criteria 12

1. E1. Oesophageal squamous cell carcinomas
2. E2. Tumor with Deficient MisMatch Repair (MMR) and/or Microsatellite Instability status
3. E3. Dihydro Pyrimidine Dehydrogenase (DPD) deficiency, NB: if not previously done, the following blood chemistry level must be perform at screening, : blood uracil level - uracilemia dosing result is mandatory prior the inclusion
4. E4. Persistent toxicities related to prior treatment of grade>1,
5. E5. QTcF longer than 450 msec for men and longer than 470 msec for women,
6. E6. Hypokalemia OR Hypomagnesemia OR Hypocalcemia Grade>1
7. E7. Contraindication to postoperative treatment (FLOT): • Known history of hypersensitivity to fluorouracil, oxaliplatin, docetaxel or calcium folinate to any of their excipients, according to the SmPCs of these products OR • Peripheral sensory neuropathy with functional impairment prior to first treatment according the SmPC of oxaliplatin OR • Clinically significant active heart disease or myocardial infarction within 6 months OR • • Recent or concomitant treatment with brivudine or recent treatment with live vaccines (minimal wash out period before randomisation: 4 weeks)
8. E8. Any concurrent chemotherapy, Investigational product for cancer treatment.
9. E9. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study
10. E10. Suspicion of serious infection
11. E11. Pregnant or breastfeeding woman
12. E12. Patient under tutorship or curatorship of deprived of liberty.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The 3-year Overall Survival (OS) rate, described as the proportion of patients still alive 3 years after the date of randomization

Secondary endpoints 7

1. • Overall survival (OS)
2. • Disease-Free Survival (DFS)
3. • Pattern and rate of relapse
4. • Tolerability profile
5. • Health-related quality of life and nutritional status, and correlation of these parameters with survival outcomes
6. A cost-effectiveness analysis of a de-escalation strategy compared to the standard postoperative chemotherapy
7. A Human and Social Sciences sub-study will be conducted in both study arms to assess if emotional competences will be predictive of HRQoL (Global Health Status dimension of the QLQ-C30) and/or supportive care needs mediated by anxio/depressive symptoms

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Leon Berard

Sponsor organisation

Centre Leon Berard

Address

28 Rue Laennec

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Centre Leon Berard

Contact name

Oncology doctor

Public contact point

Organisation

Centre Leon Berard

Contact name

Clinical Project Manager

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 1 file

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications