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Trial Title:
ViCToRy: Vorasidenib in Combination with Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas
NCT ID:
NCT05609994
Condition:
Low Grade Glioma of Brain
Conditions: Official terms:
Glioma
Conditions: Keywords:
low grade glioma
brain cancer
vorasidenib
peptide vaccine
immunotherapy
recurrent glioma
Katherine Peters
Pro00108636
IDH mutant
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PEPIDH1M vaccine + vorasidenib
Description:
Patients will receive vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids)
intramuscularly into the deltoid muscle. Patients will then receive vorasidenib 40mg
orally once a day for 28 days. After two cycles of 28-day vorasidenib and at the start of
the 3rd cycle of vorasidenib, patients will receive the PEPIDH1M vaccine intradermally
(i.d.) to alternating groin regions on the following schedule: vaccine #1, day 1; vaccine
#2, day 15. The day before vaccine #1, patients will receive a vaccine site
pre-conditioning injection of a single dose of Td toxoid. This will be administered
twelve hours to one day prior to receiving PEPIDH1M vaccine i.d. to the RIGHT groin area.
Vaccines #3 and #4 will be given on day 1 and day 15 of cycle 4. Starting on 6th cycle of
28-day vorasidenib, subjects will receive PEPIDH1M vaccine (i.d. to alternating groin
regions) every 28 days on day 1 for vaccine #5-#12. Patients will receive up to a total
of 14 cycles of vorasidenib.
Arm group label:
PEPIDH1M vaccine + vorasidenib
Summary:
The purpose of this study is to determine the safety and efficacy of a PEPIDH1M vaccine
in combination with vorasidenib, a dual inhibitor of mutant IDH1 and IDH2 enzymes, in
adult patients diagnosed with recurrent IDH1 mutant lower grade gliomas.
Detailed description:
This study is designed to assess the safety and efficacy of the PEPIDH1M vaccine in
combination with vorasidenib in adult patients recurrent IDH1 mutant lower grade gliomas.
Patients will receive vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids
adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to
the tetanus antigen. Patients will then receive vorasidenib 40 mg orally once a day for
28 days. After two cycles of 28-day vorasidenib and at the start of the 3rd cycle of
vorasidenib, patients will receive the PEPIDH1M vaccine intradermally (i.d.) to
alternating groin regions on the following schedule: vaccine #1, day 1; vaccine #2, day
15. The day before vaccine #1, patients will receive a vaccine site pre-conditioning
injection of a single dose of Td toxoid (1 flocculation unit [Lf] in a total volume of
0.4 mL saline). This will be administered twelve hours to one day prior to receiving
PEPIDH1M vaccine i.d. to the RIGHT groin area. Vaccines #3 and #4 will be given on day 1
and day 15 of cycle 4. Starting on 6th cycle of 28-day vorasidenib, subjects will receive
PEPIDH1M vaccine (i.d. to alternating groin regions) every 28 days on day 1 for vaccine
#5-#12. Patients will receive up to a total of 14 cycles of vorasidenib. Notably, a
safety lead-in will be performed before commencing on the full study to assess the safety
of the combination and evaluation for any dose-limiting toxicity (DLT).
The most common side effects of peptide vaccines are redness or swelling at the injection
site, local changes to the texture of skin (hardening) at the injection site, itching,
allergic reactions, and a potentially serious side effect called cytokine release
syndrome. The most common side effects of vorasidenib are abnormal liver function tests,
QT prolongation, stomach and/or intestinal ulcers, neurologic disturbances, skin peeling,
and isocitrate dehydrogenase (IDH) differentiation syndrome.
All patients who receive any protocol treatment will be included in either primary or
secondary efficacy analyses. Statistical analyses for the primary objective of adverse
experience will exclude patients who terminate protocol treatment prematurely (i.e., less
than 4 vaccinations) without an unacceptable toxicity.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years
2. IDH1R132H expression in primary tumor
3. Clinical and/or radiographic, progressive Grade 2-3 glioma with greater than 2 cm of
non-enhancing disease in one plane.
4. 1st recurrence only
5. Signed informed consent
6. For females of child-bearing potential, negative serum pregnancy test at screening
7. Women of childbearing potential and male participants must agree to practice
contraception
8. Karnofsky Performance Status (KPS) of ≥ 70
9. Expected survival of ≥ 12 months
10. Recovered from any clinically relevant toxicities associated with any prior surgery
for the treatment of glioma unless stabilized under medical management
11. Complete Blood Count (CBC)/differential with adequate bone marrow function as
defined below within 2 weeks of enrollment:
1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
2. Platelet count ≥ 100,000 cells/mm3
3. Hemoglobin (Hgb) ≥ 10 g/dl (Note: The use of transfusion or other intervention
to achieve Hgb ≥ 10 g/dl is acceptable.)
12. Adequate renal function as defined below within 2 weeks of enrollment:
1. Blood urea nitrogen (BUN) ≤ 25 mg/dl
2. Creatinine ≤ 1.7 mg/dl
13. Adequate hepatic function as defined below within 2 weeks of enrollment:
1. Bilirubin ≤ 2.0 mg/dl
2. Alanine transaminase (ALT) ≤ 3 x normal range
3. Aspartate aminotransferase (AST) ≤ 3 x normal range
Exclusion Criteria:
1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease
free for ≥ 3 years (e.g., carcinoma in situ of the breast, oral cavity, and cervix
are all permissible)
2. Metastases detected below the tentorium or beyond the cranial vault
3. More than 1 cm X 1 cm of enhancing disease on gadolinium contrasted MRI imaging
4. Severe, active co-morbidity, defined as follows:
1. Unstable angina and/or congestive heart failure requiring hospitalization
2. Myocardial infarction within the last 6 months.
3. Known Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for
Disease Control and Prevention (CDC) definition (Note: human immunodeficiency
virus [HIV] testing is not required for entry into this protocol. The need to
exclude patients with Acquired Immunodeficiency Syndrome (AIDS) from this
protocol is necessary because treatments involved in this protocol may be
significantly immunosuppressive.)
4. Major medical illnesses or psychiatric impairments that in the investigator's
opinion will prevent administration or completion of protocol therapy.
5. Pregnant or lactating women, due to possible adverse effects on the developing fetus
or infant due to study drug
6. Patients with a heart-rate corrected QT interval using Fridericia's formula (QTcF) ≥
450 msec or other factors that increase the risk of QT prolongation or arrhythmic
events (e.g., heart failure, hypokalemia, family history of long QT interval
syndrome)
7. Patients with known active hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection. Subjects with a sustained viral response to HCV treatment or immunity to
prior HBV infection will be permitted (Note: Patients with chronic HBV that is
adequately suppressed by institutional practice will be permitted.)
8. Patients with active gastrointestinal disease, chronic diarrhea, previous gastric
resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other
condition that limits the ingestion or gastrointestinal absorption of drugs
administered orally (Note: Gastroesophageal reflux disease under medical treatment
is allowed.)
9. Patient taking any medications that are CYP3A or CYP2C9 substrates with a narrow
therapeutic index (Note: Patients should be transferred to other medications before
receiving the first dose of study drug.)
10. Patients treated on any other therapeutic clinical protocols within 30 days prior to
study entry or during participation in the study
11. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any
component of Leukine®
12. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus
vaccine.
13. Known hypersensitivity to any component of vorasidenib
14. Prior therapy with mIDH1 targeted therapeutics
15. Unable to undergo MRI imaging
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Duke University Medical Center
Address:
City:
Durham
Zip:
27710
Country:
United States
Contact:
Last name:
Katherine Peters, MD, PhD
Phone:
919-684-5301
Email:
dukebrain1@duke.edu
Contact backup:
Last name:
Stevie Threatt
Phone:
919-684-5301
Email:
dukebrain1@duke.edu
Start date:
January 2025
Completion date:
August 2029
Lead sponsor:
Agency:
Katy Peters, MD, PhD
Agency class:
Other
Collaborator:
Agency:
Servier
Agency class:
Industry
Source:
Duke University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05609994
http://tischbraintumorcenter.duke.edu/
http://dukehealth.org/clinical-trials
http://www.dukecancerinstitute.org/
