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ATRA + PD-1 Inhibitor for Brain Tumor
Phase 2
Recruiting
Led By Stephen Bagley, MD MSCE
Research Sponsored by Stephen Bagley, MD, MSCE
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial Must have
Age 18 or older
Karnofsky performance status greater than or equal to 60
Must not have
Known active hepatitis B virus (HBsAg reactive) or active hepatitis C virus (HCV RNA detectable by PCR)
Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 84 months
Awards & highlights
Summary
This trial tests a combination of a vitamin A derivative and an immune-boosting drug in patients with recurring brain tumors. The treatment aims to normalize cancer cell behavior and enhance the immune system's ability to fight the tumor.
Who is the study for?
Adults with recurrent brain tumors (astrocytoma or oligodendroglioma) that have IDH mutations and have tried at least one chemo treatment can join. They must be able to perform daily activities, not pregnant, agree to contraception, and understand the study. Excluded are those with allergies to trial drugs, other serious illnesses, recent bevacizumab treatment, significant mass effect on the brain or active infections.
What is being tested?
The trial tests a combination of All-Trans Retinoic Acid (ATRA) and PD-1 inhibitor Retifanlimab in patients with specific recurrent brain tumors. It aims to see if this mix is safe and boosts the immune system's ability to fight cancer.
What are the potential side effects?
Possible side effects include allergic reactions to ATRA or Retifanlimab components, increased risk of infection due to immune suppression from treatments, lung issues like pneumonitis or interstitial lung disease, and potential autoimmune responses.
Eligibility Criteria
Inclusion Criteria
You may be eligible if you check “Yes” for the criteria belowSelect...
I am 18 years old or older.
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I can care for myself but may not be able to do active work.
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I have a confirmed diagnosis of astrocytoma or oligodendroglioma that has worsened or returned after chemotherapy.
Select...
I haven't used 5-ALA for surgery because it reacts with my ATRA treatment.
Select...
I understand the study and agree to participate by signing the consent form.
Exclusion Criteria
You may be eligible for the trial if you check “No” for criteria below:Select...
I have active hepatitis B or C.
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I am taking high doses of steroids for an autoimmune disease.
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I have not taken bevacizumab in the last 3 months.
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My cancer has spread to the lining of my brain and spinal cord.
Select...
I have serious heart problems that are not under control.
Select...
I have or had lung scarring or inflammation not caused by an infection.
Select...
I have a tumor in my brainstem or spinal cord that shows up on scans, but I don't have a known tumor in my spinal cord.
Select...
I do not have another cancer that could affect this trial's safety or results.
Select...
I am allergic to tretinoin or similar medications.
Select...
I am HIV-positive and currently on antiretroviral therapy.
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I have a significant brain swelling or shift.
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I had severe side effects from previous immunotherapy that required stopping the treatment.
Select...
I am not allergic to retifanlimab or its ingredients.
Select...
I have had a solid organ or bone marrow transplant.
Timeline
Screening ~ 3 weeks3 visits
Treatment ~ Varies
Follow Up ~ 84 months
Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~84 months
Treatment Details
Study Objectives
Study objectives can provide a clearer picture of what you can expect from a treatment.Primary study objectives
Objective radiographic response (ORR)
Secondary study objectives
Incidence of Treatment-Emergent Adverse Events as assessed by NCI CTCAE v 5.0
Overall survival
Progression Free Survival
Side effects data
From 2021 Phase 2 trial • 94 Patients • NCT0359729523%
Asthenia
21%
Diarrhoea
18%
Fatigue
16%
Nausea
16%
Anaemia
15%
Vomiting
13%
Constipation
13%
Decreased appetite
12%
Pruritus
12%
Cough
12%
Dyspnoea
11%
Pyrexia
10%
Hypothyroidism
10%
Rectal haemorrhage
9%
Arthralgia
9%
Back pain
9%
Headache
9%
Weight decreased
7%
Urinary tract infection
7%
Proctalgia
7%
Aspartate aminotransferase increased
7%
Abdominal pain
6%
Insomnia
5%
Hypokalaemia
5%
Rash
5%
Cystitis
3%
General physical health deterioration
3%
Pelvic pain
2%
Hypercalcaemia
2%
Inadequate analgesia
2%
Intestinal obstruction
2%
Haematuria
2%
Pleural effusion
2%
Sepsis
2%
Pneumonia
1%
Mental status changes
1%
Proctitis haemorrhagic
1%
Pseudomonas infection
1%
Purpura
1%
Respiratory failure
1%
Acute kidney injury
1%
Anal abscess
1%
Gastroenteritis
1%
Interstitial lung disease
1%
Pancreatic carcinoma
1%
Adrenal insufficiency
1%
Hydronephrosis
1%
Ileus
1%
Flank pain
1%
Immune-mediated enterocolitis
1%
Large intestinal obstruction
1%
Pain
1%
Acute respiratory failure
1%
Cholecystitis acute
1%
Lyme disease
1%
Lymphangiosis carcinomatosa
1%
Herpes zoster
1%
Hepatitis
1%
Pelvic infection
1%
Peritonitis
1%
Blood bilirubin increased
1%
Body temperature increased
1%
Bone pain
1%
Cellulitis
1%
Cholangitis
1%
Cholecystitis
1%
Cognitive disorder
1%
Colonic fistula
1%
Coma hepatic
1%
Dehydration
1%
Device related infection
1%
Diffuse large B-cell lymphoma
1%
Fall
1%
Femur fracture
1%
Gastric ulcer
1%
Skin infection
1%
Stoma site infection
1%
Superior mesenteric artery syndrome
1%
Thrombosis
1%
Transitional cell carcinoma
1%
Tumour embolism
1%
Tumour pain
1%
Ureteric compression
1%
Urinary retention
1%
Venous thrombosis limb
1%
Pulmonary embolism
1%
Catheter site pain
1%
Pneumocystis jirovecii pneumonia
100%
80%
60%
40%
20%
0%
Study treatment Arm
Retifanlimab 500 mg
Trial Design
4Treatment groups
Experimental Treatment
Group I: Arm D (surgical arm, ATRA + retifanlimab pre-operatively)Experimental Treatment2 Interventions
Subject in Arm D will receive the combination of ATRA 45mg/m2/day orally in two equally divided doses for 14 days pre-surgery plus a 500mg IV dose of retifanlimab 14 days prior to the date of surgery. Following surgery all patients will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1-14 and retifanlimab 500mg IV on day 1.
Group II: Arm C (surgical arm, ATRA alone pre-operatively)Experimental Treatment2 Interventions
Subject in Arm C will receive ATRA 45mg/m2/day orally in two equally divided doses for 14 days pre-surgery, then undergo surgery. Following surgery all patients will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1-14 and retifanlimab 500mg IV on day 1.
Group III: Arm B (failed only one prior alkylating chemotherapy)Experimental Treatment2 Interventions
Subject in Arm B are patients who have failed only one prior alkylating chemotherapy regimen and have gone at least 12 months since the last treatment. Subjects in Arm B will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1 through 14 and retifanlimab 500mg IV on day 1.
Group IV: Arm A (failed prior TMZ + one other alkylating chemotherapy)Experimental Treatment2 Interventions
Subjects in Arm A are alkylator-refractory and at high risk for progression of disease, have failed temozolmide and another alkylating agent. Subjects in Arm A will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1 through 14 and retifanlimab 500mg IV on day 1.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
All-trans retinoic acid
2012
Completed Phase 3
~1050
Retifanlimab
2018
Completed Phase 2
~320
Research Highlights
Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Common treatments for Isocitrate Dehydrogenase (IDH) mutations include All-Trans Retinoic Acid (ATRA) and PD-1 inhibitors like Retifanlimab. ATRA works by inducing differentiation and apoptosis in cancer cells, thereby reducing their proliferation.
PD-1 inhibitors enhance the immune response by blocking the PD-1 pathway, which cancer cells use to evade immune detection. These treatments are significant for IDH-mutant patients as they directly target cancer cells and boost the body's immune system to combat the tumor more effectively.
Photopheresis--extracorporeal irradiation of 8-MOP containing blood--a new therapeutic modality.Co-Therapy of Albendazole and Dexamethasone Reduces Pathological Changes in the Cerebral Parenchyma of Th-1 and Th-2 Dominant Mice Heavily Infected with <i>Angiostrongylus cantonensis</i>: Histopathological and RNA-seq Analyses.An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors.
Photopheresis--extracorporeal irradiation of 8-MOP containing blood--a new therapeutic modality.Co-Therapy of Albendazole and Dexamethasone Reduces Pathological Changes in the Cerebral Parenchyma of Th-1 and Th-2 Dominant Mice Heavily Infected with <i>Angiostrongylus cantonensis</i>: Histopathological and RNA-seq Analyses.An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors.
Find a Location
Who is running the clinical trial?
University of PennsylvaniaOTHER
2,062 Previous Clinical Trials
42,711,757 Total Patients Enrolled
Stephen Bagley, MD, MSCELead Sponsor
1 Previous Clinical Trials
10 Total Patients Enrolled
Incyte CorporationIndustry Sponsor
386 Previous Clinical Trials
57,918 Total Patients Enrolled
Media Library
Eligibility Criteria:
This trial includes the following eligibility criteria:- My MRI shows my tumor is either larger than 1cmx1cm or has grown by at least 25% since my last treatment.My tumor has a confirmed IDH1 or IDH2 mutation.I have tried temozolomide or another similar drug without success.I have tried temozolomide and another alkylator drug without success.I am 18 years old or older.I have active hepatitis B or C.I haven't taken immunosuppressive drugs, except steroids, in the last 6 months.I am taking high doses of steroids for an autoimmune disease.I can have an MRI with contrast and haven't increased my steroid dose in 5 days.I can swallow pills.I do not have any serious health issues that could worsen with this study's treatment.I have not taken bevacizumab in the last 3 months.I can care for myself but may not be able to do active work.My organs and bone marrow are working well.I have had or will have genetic testing for 1p/19q and MGMT before joining.I have not received a live vaccine in the last 28 days.I have recovered from the major side effects of my previous cancer treatments.I have tried temozolomide and another alkylator without success.My cancer has spread to the lining of my brain and spinal cord.I have serious heart problems that are not under control.I have or had lung scarring or inflammation not caused by an infection.I have a tumor in my brainstem or spinal cord that shows up on scans, but I don't have a known tumor in my spinal cord.My MRI shows my tumor is either larger than 1cm or has grown by at least 25% since my last treatment.I do not have another cancer that could affect this trial's safety or results.I am allergic to tretinoin or similar medications.I am HIV-positive and currently on antiretroviral therapy.I have had multiple relapses and treatments for my condition.My doctors recommend surgery for my possibly returning or worsening tumor.I have a significant brain swelling or shift.I have tried temozolomide or another similar drug without success.I've had one chemotherapy treatment that didn't work and it's been over a year since my last treatment.I had severe side effects from previous immunotherapy that required stopping the treatment.I am not allergic to retifanlimab or its ingredients.I have had a solid organ or bone marrow transplant.I have a confirmed diagnosis of astrocytoma or oligodendroglioma that has worsened or returned after chemotherapy.My tumor has a confirmed IDH1 or IDH2 mutation.I haven't used 5-ALA for surgery because it reacts with my ATRA treatment.I understand the study and agree to participate by signing the consent form.My glioma has worsened after chemotherapy, possibly including temozolomide or lomustine.
Research Study Groups:
This trial has the following groups:- Group 1: Arm B (failed only one prior alkylating chemotherapy)
- Group 2: Arm C (surgical arm, ATRA alone pre-operatively)
- Group 3: Arm D (surgical arm, ATRA + retifanlimab pre-operatively)
- Group 4: Arm A (failed prior TMZ + one other alkylating chemotherapy)
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.
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