Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

Capecitabine

Antimetabolites

LCRT: Long-course pelvic radiotherapy given concomitantly with capecitabine chemotherapy and TOLINAPANT (ASTX660):

* mFOLFIRINOX will be given prior to tolinapant (ASTX660) for 6 cycles over 12 weeks;
* Pelvic radiotherapy to a planned volume at a 50-Gy total dose in 25 daily fractions of 2 Gy (5 days per week from Monday to Friday) for 5 weeks;
* Chemotherapy (capecitabine) at 800 mg/m2 bid for 5 days per week (From Monday to Friday) for 25 days will be given concomitantly during the 5 weeks of radiotherapy;
* TOLINAPANT (ASTX660) starting from 14 days before the first dose of radiotherapy, for 10 weeks. Tolinapant (ASTX660) will be given concomitantly with RT and chemotherapy for 5 weeks.

SCRT: Short course pelvic radiotherapy followed by chemotherapy in combination with TOLINAPANT (ASTX660):

* Pelvic radiotherapy will be given to a planned volume at a total dose of 25 Gy, in 5 daily fractions of 5 Gy for 1 week (5 days from Monday-Friday)
* Chemotherapy (FOLFOX4): given every 2 weeks for 9 cycles, starting 10 days after the last session of short course radiotherapy. Alternative: CAPOX given every 3 weeks for 6 cycles, starting 10 days after the last session of short course radiotherapy.
* Tolinapant (ASTX660) starting from 14 days before the first dose of radiotherapy, for 10 weeks. Tolinapant (ASTX660) will be given concomitantly with RT for 5 days.

prior to tolinapant (ASTX660) for 6 cycles over 12 weeks

mFOLFIRINOX

50-Gy total dose in 25 daily fractions of 2 Gy (5 days per week from Monday to Friday) for 5 weeks

Pelvic radiotherapy LCRT

800 mg/m2 bid for 5 days per week (From Monday to Friday) for 25 days will be given concomitantly during the 5 weeks of radiotherapy

starting from 14 days before the first dose of radiotherapy, for 10 weeks.

TOLINAPANT (ASTX660)

total dose of 25 Gy, in 5 daily fractions of 5 Gy for 1 week (5 days from Monday-Friday)

Pelvic radiotherapy SCRT

given every 2 weeks for 9 cycles, starting 10 days after the last session of short course radiotherapy

FOLFOX4

every 3 weeks for 6 cycles, starting 10 days after the last session of short course radiotherapy.

CAPOX

Eric DEUTSCH, MD, PhD

Catherine RICHON

Jessica SERRAND, MD

Alexandra LAURET

Eric DEUTSCH, Md, PhD

Compare two arms:

* Chemotherapy followed by tolinapant (ASTX660) in combination with Long-Course Radio Chemotherapy (LCRT), and
* Tolinapant (ASTX660) in combination with Short-Course Radiotherapy (SCRT) followed by chemotherapy For each patient, the treatment arm will be allocated on the following basis: patients will be allocated to the chemotherapy followed by LCRT arm unless they present at least one of the following criteria: contraindication to receive mFOLFIRINOX (including intolerance to irinotecan and UGT1A1\*28 polymorphism), age \> 75, general condition incompatible with the radiotherapy schedule of LCRT. In such case, patients will be allocated to the SCRT arm.

Tolinapant (ASTX660) will be administered orally once a day for 7 consecutive days every other week during 10 weeks (One week On / One week Off during 10 weeks).

Both treatment arms will have a dose escalation part to determine the MTD and/or RP2D, followed by an expansion part where up to 21 subjects will be dosed at the RP2D. Both arms will enroll simultaneously.

Comparative phase 1b trial with randomization

Preoperative Radiotherapy And ASTX660 in Rectum Cancer

An Open-Label Multicenter Phase 1b Study of Tolinapant (ASTX660) in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Patients With Rectum Cancer (PRAAR 1: Preoperative Radiotherapy And ASTX660 in Rectum Cancer)

ASTX660-related toxicities graded using NCI CTCAE V5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Preoperative Radiotherapy And ASTX660 in Rectum Cancer	NCT05912075	Locally-advance...	mFOLFIRINOX Pelvic radiothe... Capecitabine TOLINAPANT (AST... Pelvic radiothe... FOLFOX4 CAPOX	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris
Preoperative Radiotherapy And ASTX660 in Rectum Cancer	NCT05912075	Locally-advance...	mFOLFIRINOX Pelvic radiothe... Capecitabine TOLINAPANT (AST... Pelvic radiothe... FOLFOX4 CAPOX	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris

Spots Global Cancer Trial Database for pelvic radiotherapy scrt