NCT05912075: PRAAR1

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)

Recruiting now Phase 1 Last updated 7 February 2024

What this trial tests

Phase 1 trial testing mFOLFIRINOX in Locally-advanced Rectal Cancer in 78 participants. Currently enrolling.

Timeline

19 December 2023

Primary endpoint
1 January 2028

1 January 2029

Quick facts

Lead sponsor	Gustave Roussy, Cancer Campus, Grand Paris
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	78
Start date	19 December 2023
Primary completion	1 January 2028
Estimated completion	1 January 2029
Sites	2 locations across France

Drugs / interventions tested

• mFOLFIRINOX
• Pelvic radiotherapy LCRT
• Capecitabine (capecitabine) — full drug profile →
• TOLINAPANT (ASTX660) — full drug profile →
• Pelvic radiotherapy SCRT
• FOLFOX4 — full drug profile →
• CAPOX — full drug profile →

Conditions studied

• Locally-advanced Rectal Cancer — all drugs for Locally-advanced Rectal Cancer →

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris — full company profile →

Who can join

18 and older, any sex, with Locally-advanced Rectal Cancer. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Dose-limiting toxicities (DLTs)
  Time frame: during the 10 weeks of tolinapant (ASTX660) treatment
  ASTX660-related toxicities graded using NCI CTCAE V5.0

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting Inhibitor of Apoptosis Proteins to Overcome Chemotherapy Resistance-A Marriage between Targeted Therapy and Cytotoxic Chemotherapy.
   Barroso T, Melo-Alvim C, Ribeiro LA, Casimiro S, et al · · 2023 · cited 11× · PMID 37686191 · DOI 10.3390/ijms241713385
2. IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.
   Teng Z, Teng L, Xie J. · · 2026 · PMID 41501908 · DOI 10.1186/s12967-025-07640-7