Non inferiority study of preoperative chemotherapy without pelvic irradiation for rectal cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

5 Jun 2019 → ongoing

Decision date (initial)

2024-05-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-510580-28-00

EudraCT number

2018-002717-35

ClinicalTrials.gov

NCT03875781

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To demonstrate the non-inferiority of preoperative chemotherapy only compared to chemotherapy followed by chemoradiotherapy on oncologic outcomes in locally advanced resectable low or middle rectal cancer (cT3N0 and/or cT1-T3N+)

Conditions and MedDRA coding

Middle or low locally advanced resectable rectal carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically proven middle or low rectal carcinoma, ≤ 12 cm from the anal verge on MRI (sagittal slide)
2. cT3N0 and/or cT1-T3N+ on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound)
3. Pretreatment predictive circumferential margin > 2mm on pretreatment imaging work up (pelvic contrast enhanced MRI)
4. Patients must be 18 years old or older
5. A World Health Organization (WHO/ECOG) performance status of 0 or 1
6. Informed consent signed
7. Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 6 months after the last study treatment

Exclusion criteria 21

1. Rectal tumor > 12 cm from the anal verge on MRI (sagittal slide)
2. cT4 tumor on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound) or involvement of external sphincter
3. Circumferential margin ≤ 2 mm on pretreatment imaging work up (pelvic contrast enhanced MRI)
4. Metastatic disease
5. Prior pelvic irradiation or any contraindication to pelvic irradiation
6. Contraindication to oxaliplatin or irinotecan or 5FU based chemotherapy
7. Concomitant treatment with warfarin is contraindicated and warafarin must be replaced whenever possible to allow for inclusion
8. Recent or concomitant treatment with brivudine is contraindicated
9. Contraindications to 5-FU: complete and permanent insufficiency in dihydropyrimidine dehydrogenase, bone marrow insufficiency, chronic and severe infection
10. Contraindication to irinotecan : inflammatory bowel disease, bilirubin serum level > 3 times the upper limit of the normal rate, severe bone marrow insufficiency, WHO/ECOG performence status > 2
11. Concomitant treatment with millepertuis
12. Contraindication to oxaliplatin : bone marrow insufficiency before treatment initiation (neutrophil count <2x109/L and/or platelet count <100x109/L), peripheral neuropathy with permanent invalidity before treatment initiation
13. Contraindications to folinic acid : Biermer anemia and other anemia related to B12 vitamin insufficiency
14. Contraindications to capecitabine : severe renal insufficiency (Creatinin clearance <30 ml/min), complete and permanent insufficiency in dihydropyrimidine dehydrogenase
15. Live attenuated vaccine should not be used during and 6 months after preoperative treatment
16. Previous colorectal cancer
17. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years
18. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
19. Protected adults
20. Pregnancy or breastfeeding
21. Patient with no national health or universal plan affiliation coverage

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main endpoint of this phase III study is 3-year progression-free survival from the time to randomization.

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Project Manager

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Project Manager

Locations

1 EU/EEA country · 46 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 8 files

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

Application history

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