search
Back to results

ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas (ViCToRy)

Primary Purpose

Low Grade Glioma of Brain

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PEPIDH1M vaccine + vorasidenib
Sponsored by
Katy Peters, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Low Grade Glioma of Brain focused on measuring low grade glioma, brain cancer, vorasidenib, peptide vaccine, immunotherapy, recurrent glioma, Katherine Peters, Pro00108636, IDH mutant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18 years IDH1R132H expression in primary tumor Clinical and/or radiographic, progressive Grade 2-3 glioma with greater than 2 cm of non-enhancing disease in one plane. 1st recurrence only Signed informed consent For females of child-bearing potential, negative serum pregnancy test at screening Women of childbearing potential and male participants must agree to practice contraception Karnofsky Performance Status (KPS) of ≥ 70 Expected survival of ≥ 12 months Recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management Complete Blood Count (CBC)/differential with adequate bone marrow function as defined below within 2 weeks of enrollment: Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 100,000 cells/mm3 Hemoglobin (Hgb) ≥ 10 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.) Adequate renal function as defined below within 2 weeks of enrollment: Blood urea nitrogen (BUN) ≤ 25 mg/dl Creatinine ≤ 1.7 mg/dl Adequate hepatic function as defined below within 2 weeks of enrollment: Bilirubin ≤ 2.0 mg/dl Alanine transaminase (ALT) ≤ 3 x normal range Aspartate aminotransferase (AST) ≤ 3 x normal range Exclusion Criteria: 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) Metastases detected below the tentorium or beyond the cranial vault More than 1 cm X 1 cm of enhancing disease on gadolinium contrasted MRI imaging Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization Myocardial infarction within the last 6 months. 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.) Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug 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) 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.) 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.) 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.) Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine® Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus vaccine. Known hypersensitivity to any component of vorasidenib Prior therapy with mIDH1 targeted therapeutics Unable to undergo MRI imaging

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PEPIDH1M vaccine + vorasidenib

Arm 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.

Outcomes

Primary Outcome Measures

To assess the safety of the PEPIDH1M vaccine in combination vorasidenib in adult patients with progressive IDH1 mutant World Health Organization (WHO) Grade 2-3 gliomas
The proportion of patients with an unacceptable toxicity
Describe the efficacy, as measured by progression-free survival (PFS), of the combination of PEPIDH1M vaccine and vorasidenib in adult patients with recurrent IDH1 lower grade glioma
The time between initiation of cycle 1 vorasidenib and first documentation of disease progression or death

Secondary Outcome Measures

Full Information

First Posted
November 2, 2022
Last Updated
August 22, 2023
Sponsor
Katy Peters, MD, PhD
Collaborators
Servier
search

1. Study Identification

Unique Protocol Identification Number
NCT05609994
Brief Title
ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas
Acronym
ViCToRy
Official Title
ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Katy Peters, MD, PhD
Collaborators
Servier

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Low Grade Glioma of Brain
Keywords
low grade glioma, brain cancer, vorasidenib, peptide vaccine, immunotherapy, recurrent glioma, Katherine Peters, Pro00108636, IDH mutant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PEPIDH1M vaccine + vorasidenib
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
PEPIDH1M vaccine + vorasidenib
Intervention 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.
Primary Outcome Measure Information:
Title
To assess the safety of the PEPIDH1M vaccine in combination vorasidenib in adult patients with progressive IDH1 mutant World Health Organization (WHO) Grade 2-3 gliomas
Description
The proportion of patients with an unacceptable toxicity
Time Frame
3.5 years
Title
Describe the efficacy, as measured by progression-free survival (PFS), of the combination of PEPIDH1M vaccine and vorasidenib in adult patients with recurrent IDH1 lower grade glioma
Description
The time between initiation of cycle 1 vorasidenib and first documentation of disease progression or death
Time Frame
10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years IDH1R132H expression in primary tumor Clinical and/or radiographic, progressive Grade 2-3 glioma with greater than 2 cm of non-enhancing disease in one plane. 1st recurrence only Signed informed consent For females of child-bearing potential, negative serum pregnancy test at screening Women of childbearing potential and male participants must agree to practice contraception Karnofsky Performance Status (KPS) of ≥ 70 Expected survival of ≥ 12 months Recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management Complete Blood Count (CBC)/differential with adequate bone marrow function as defined below within 2 weeks of enrollment: Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 100,000 cells/mm3 Hemoglobin (Hgb) ≥ 10 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.) Adequate renal function as defined below within 2 weeks of enrollment: Blood urea nitrogen (BUN) ≤ 25 mg/dl Creatinine ≤ 1.7 mg/dl Adequate hepatic function as defined below within 2 weeks of enrollment: Bilirubin ≤ 2.0 mg/dl Alanine transaminase (ALT) ≤ 3 x normal range Aspartate aminotransferase (AST) ≤ 3 x normal range Exclusion Criteria: 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) Metastases detected below the tentorium or beyond the cranial vault More than 1 cm X 1 cm of enhancing disease on gadolinium contrasted MRI imaging Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization Myocardial infarction within the last 6 months. 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.) Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug 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) 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.) 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.) 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.) Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study Patients with known hypersensitivity to GM-CSF, yeast-derived products, or any component of Leukine® Allergy or hypersensitivity to tetanus vaccine or any component of the tetanus vaccine. Known hypersensitivity to any component of vorasidenib Prior therapy with mIDH1 targeted therapeutics Unable to undergo MRI imaging
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katherine Peters, MD, PhD
Phone
919-684-5301
Email
dukebrain1@duke.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Stevie Threatt
Phone
919-684-5301
Email
dukebrain1@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine Peters, MD, PhD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katherine Peters, MD, PhD
Phone
919-684-5301
Email
dukebrain1@duke.edu
First Name & Middle Initial & Last Name & Degree
Stevie Threatt
Phone
919-684-5301
Email
dukebrain1@duke.edu

12. IPD Sharing Statement

Links:
URL
http://tischbraintumorcenter.duke.edu/
Description
The Preston Robert Tisch Brain Tumor Center at Duke
URL
http://dukehealth.org/clinical-trials
Description
Duke Health
URL
http://www.dukecancerinstitute.org/
Description
Duke Cancer Institute

Learn more about this trial

ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas

We'll reach out to this number within 24 hrs