Preoperative Radiotherapy And ASTX660 in Rectum Cancer
ConditionLocally-advanced Rectal Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorGustave Roussy, Cancer Campus, Grand Paris
About this trial
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.
Eligibility criteria
Qualifiers
a distance between the tumor or its lymph node and the mesorectal fascia ≤ 2 mm on the pelvic MRI at diagnosis.
*and/or N2
No evidence of metastatic disease on CT-scan (chest and abdomen), including resectable metastases
Age : ≥ 18 years old at the time of informed consent
Disqualifiers
Any contraindications to MRI (e.g. subjects with pacemakers, claustrophobia, excessive weight, etc).
Participation in another clinical study with an investigational product during the last 3 months.
No other anticancer therapy during study participation. (however, informed consent can be signed during mFOLFIRINOX for patients willing to enter the LCRT arm).
5-FU, capecitabine and known dihydropyrimidine dehydrogenase (DPD) deficiency, or
Trial design
Treatments tested in this trial
- mFOLFIRINOX
- Pelvic radiotherapy LCRT
- Capecitabine
- TOLINAPANT (ASTX660)
- Pelvic radiotherapy SCRT
- FOLFOX4
- CAPOX
Treatment groups
78 Participants
are divided into 2 treatment groupsSponsors and collaborators
Source ClinicalTrials.gov