Health TrialsbyHealthPanel

All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma

ConditionsGliomaIDH MutationAstrocytomaOligodendroglioma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorStephen Bagley, MD, MSCE

About this trial

This is a Phase II study of the combination of All-Trans Retinonic Acid (ATRA) and PD-1 inhibition (Retifanlimab) in patient with recurrent IDH-mutant glioma. The Sponsor-Investigator hypothesizes that the proposed regimen will be safe and stimulate a robust anti-tumor immune response.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Prior histopathologically proven diagnosis of astrocytoma (grade 2-4) or oligodendroglioma (grade 2-3) according to the World Health Organization (WHO) 2021 Classification System that is progressive or recurrent following at least one prior alkylating chemotherapy regimen (i.e., temozolomide and/or lomustine), +/- radiation therapy

Patient's tumor must have a known mutation in IDH1 or IDH2. IDH1/2 mutation status must be confirmed by DNA sequencing and could have been performed in any CLIA/CAP-certified laboratory. IDH1/2 mutational testing could have been performed on patient's tumor either at initial diagnosis or on a subsequent recurrent tumor.

All Safety Run-In and Phase 2 patients: patients with any contrast-enhancing tumor must have measurable disease per RANO criteria (defined by at least 1cmx1cm of contrast-enhancing tumor). Patients with exclusively non-enhancing tumors must have least a 25% increase in bi-dimensional product of FLAIR signal abnormality (measurable disease) compared to the patient's best MRI scan (smallest bi-dimensional product of FLAIR signal abnormality) obtained following completion of the patient's most recent line of therapy

Safety Run-In: Must have failed temozolomide OR another alkylator (e.g. lomustine, procarbazine, carmustine). May have failed an unlimited number of prior systemic regimens, +/- prior radiotherapy.

Disqualifiers

Contrast-enhancing tumor in brainstem or spinal cord (subjects do not need spinal MRI for screening, but known spinal cord tumor is exclusionary)

Diffuse leptomeningeal disease

Patients who have received bevacizumab within the last 3 months are ineligible

Patients with clinically significant mass effect or midline shift (e.g., 1-2 cm of midline shift)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Retifanlimab

    Drug

    Administered 500mg IV on day 1 of every 28-day cycle, continued until disease progression, unacceptable toxicity, or 2 years from the first dose of study medication, whichever occurs first.

  • All-trans retinoic acid

    Drug

    All-trans retinoic acid (ATRA) 45mg/m2 orally in two equally divided doses on days 1-14 of each 28-day cycle, continued until disease progression, unacceptable toxicity, or 2 years from the first dose of study medication, whichever occurs first.

Treatment groups

55 Participants
are divided into 4 treatment groups
Group A: Arm A (failed prior TMZ + one other alkylating chemotherapy)Experimental treatment 2 interventions
Group B: Arm B (failed only one prior alkylating chemotherapy)Experimental treatment 2 interventions
Group C: Arm C (surgical arm, ATRA alone pre-operatively)Experimental treatment 2 interventions
Group D: Arm D (surgical arm, ATRA + retifanlimab pre-operatively)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Objective radiographic response (ORR)

Objective radiographic response (ORR), as measured by modified Response Assessment in Neuro-Oncology (RANO) criteria. ). The response is classified as Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).

Time frame
26 months

Secondary outcomes

1

Incidence of Treatment-Emergent Adverse Events as assessed by NCI CTCAE v 5.0

Adverse events will be evaluated by monitoring frequency, duration, and severity of adverse events (AEs) per NCI CTCAE v 5.0

Time frame
25 months
2

Progression Free Survival

PFS, defined as the time from date of enrollment until the earliest date of disease progression (as determined by modified RANO criteria) or death due to any cause

Time frame
84 months
3

Overall survival

OS, defined as the time from date of enrollment until death from any cause

Time frame
84 months

Other outcomes

Sponsors and contacts

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

Stephen Bagley, MD, MSCE

Lead sponsor

Abramson Cancer Center at Penn Medicine

Sponsor institution

Incyte Corporation

Collaborator

Abramson Cancer Center at Penn Medicine

Collaborator

Source ClinicalTrials.gov
Apply now