NCT05912075

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)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 78 (estimated)
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Locally-advanced Rectal Cancer

Interventions

Type	Name	Description
DRUG	mFOLFIRINOX	prior to tolinapant (ASTX660) for 6 cycles over 12 weeks
RADIATION	Pelvic radiotherapy LCRT	50-Gy total dose in 25 daily fractions of 2 Gy (5 days per week from Monday to Friday) for 5 weeks
DRUG	Capecitabine	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
DRUG	TOLINAPANT (ASTX660)	starting from 14 days before the first dose of radiotherapy, for 10 weeks.
RADIATION	Pelvic radiotherapy SCRT	total dose of 25 Gy, in 5 daily fractions of 5 Gy for 1 week (5 days from Monday-Friday)
DRUG	FOLFOX4	given every 2 weeks for 9 cycles, starting 10 days after the last session of short course radiotherapy
DRUG	CAPOX	every 3 weeks for 6 cycles, starting 10 days after the last session of short course radiotherapy.

Timeline

• Start date: 2023-12-19
• Primary completion: 2028-01-01
• Completion: 2029-01-01
• First posted: 2023-06-22
• Last updated: 2024-02-08

Locations

2 sites across 1 country: France