Study on All-Trans Retinoic Acid (ATRA) and PD-1 Inhibitor for Recurrent IDH-Mutant Glioma

Sponsor: Stephen Bagley, MD, MSCE

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT05345002

Provider View

This clinical trial is testing a combination of All-Trans Retinoic Acid (ATRA) and a PD-1 inhibitor called Retifanlimab to see if it is safe and can effectively stimulate the immune system to fight recurrent IDH-mutant glioma, a type of brain tumor.

Patient Parameters

Program Overview

This Phase II study is exploring whether a combination of All-Trans Retinoic Acid (ATRA) and a PD-1 inhibitor, Retifanlimab, can safely and effectively boost the immune response against recurrent IDH-mutant glioma, a type of brain tumor. The study includes different parts: a Safety Run-In to test initial safety, a Phase 2 portion to further evaluate the treatment, and a Surgical Portion for patients undergoing surgery.

Description

The study is divided into three parts: Safety Run-In, Phase 2, and a Surgical Portion.

  • Safety Run-In: Participants receive treatment in 28-day cycles, with ATRA taken orally twice a day for 14 days and Retifanlimab given by IV on day 1. This part ensures the treatment is safe before moving to the next phases.

  • Phase 2: All participants receive the same 28-day cycle treatment as in the Safety Run-In.

    • Arm A: Includes patients whose cancer has not responded to certain chemotherapy drugs. If no response is seen in the first 12 patients, this part will stop.
    • Arm B: Includes patients who have failed one prior chemotherapy and have been off treatment for at least 12 months. If at least 5 out of 14 patients respond, this part will continue.

  • Surgical Portion: Patients eligible for surgery are randomly assigned to receive either ATRA alone or ATRA with Retifanlimab before surgery. After surgery, all patients receive the same 28-day cycle treatment.

The study aims to collect fresh tumor tissue during surgery for further analysis and to continue treatment post-surgery to evaluate the effectiveness of the combination therapy.

Eligibility Criteria

Inclusion Criteria

  • Have a confirmed diagnosis of astrocytoma or oligodendroglioma that has returned or progressed after previous treatment.
  • Tumor must have a specific IDH1 or IDH2 mutation.
  • Must have measurable disease or specific changes in MRI scans.
  • Must have failed certain chemotherapy treatments.
  • Surgical candidates must need surgery for tumor recurrence.
  • Must have specific genetic tests done on the tumor.
  • Must be able to undergo MRI scans.
  • Must have recovered from previous treatments.
  • Must be able to swallow pills.
  • Must be 18 years or older.
  • Must have a life expectancy of more than 3 months.
  • Must have adequate organ and blood function.
  • Women of childbearing potential must have a negative pregnancy test and agree to use contraception.
  • Must be able to understand and agree to the study procedures.

Exclusion Criteria

  • Tumor in the brainstem or spinal cord.
  • Diffuse leptomeningeal disease.
  • Recent treatment with bevacizumab.
  • Significant brain swelling or shift.
  • Use of immunosuppressive medications other than steroids.
  • History of immunodeficiency or organ transplant.
  • Active autoimmune disease requiring high-dose steroids.
  • Lung disease or pneumonitis.
  • Previous severe immune-related side effects from similar treatments.
  • Active hepatitis B or C, or HIV.
  • Other serious medical conditions or uncontrolled infections.
  • Significant heart disease.
  • Allergies to study drugs.
  • Pregnant or breastfeeding women.
  • Recent live vaccine.
  • Participation in another clinical trial.

Get This Program In Your Inbox

Receive detailed information about this treatment opportunity to review with your healthcare provider.