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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

This trial does not accept healthy volunteers

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

Design model

Parallel

Treatments tested in this trial

  • mFOLFIRINOX

    Drug

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

  • Pelvic radiotherapy LCRT

    Radiation

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

  • Capecitabine

    Drug

    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)

    Drug

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

  • Pelvic radiotherapy SCRT

    Radiation

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

  • FOLFOX4

    Drug

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

  • CAPOX

    Drug

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

Treatment groups

78 Participants
are divided into 2 treatment groups
Group A: LCRTExperimental treatment 4 interventions
Group B: SCRTExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Dose-limiting toxicities (DLTs)

ASTX660-related toxicities graded using NCI CTCAE V5.0

Time frame
during the 10 weeks of tolinapant (ASTX660) treatment

Secondary outcomes

1

Overall survival

Time frame
2 years after surgery
2

Disease-free survival (DFS)

Time frame
2 years after surgery
3

Local recurrence-free survival

Time frame
2 years after surgery
4

Distant metastasis-free survival

Time frame
2 years after surgery

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Gustave Roussy, Cancer Campus, Grand Paris

Lead sponsor

Source ClinicalTrials.gov
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