Recurrent IDH1R132H-mutant Astrocytoma, Grade 2 - 4Phase 1iVOCALNCT07877415
A Multicenter Safety and Immunogenicity Window-of-opportunity Phase 1 Interventional Trial Assessing the Combination of IDH1 Vaccine (IDH1-vac) and Vorasidenib in Adult Patients With Recurrent IDH1R132H-mutant Astrocytoma, Grade 2 - 4 (iVOCAL)
A Phase 1 study testing IDH1R132H-vac, Vorasidenib 40 mg Oral Tablet and Aldara - Imiquimod 5% in people with Recurrent IDH1R132H-mutant Astrocytoma, Grade 2 - 4, run by Heidelberg University.
Trial summary
The study aims to investigate the combination of the IDH1R132H peptide vaccine and the dual IDH1/2 inhibitor vorasidenib in patients with recurrent and/or progressive astrocytoma, WHO grade 2,3 and 4. The trial will assess the safety, and immunogenicity of the combined treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent IDH1R132H-mutant Astrocytoma, Grade 2 - 4
- What is being tested?
- IDH1R132H-vac, Vorasidenib 40 mg Oral Tablet and Aldara - Imiquimod 5%
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to 31 Dec 2033
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability of patient to understand character and individual consequences of the clinical trial
- Written informed consent
- Age ≥ 18 years
- Patients present with unequivocal first, second or third recurrence of a histologically and molecularly confirmed IDH1R132H-mutated astrocytoma WHO grade 2, 3 and 4 recurrent and/or progressive after radiotherapy and chemotherapy
- Availability of pre-study MRI (not older than 3 months) of latest tumor recurrence
- Availability of tumor tissue from the most recent glioma-directed surgical intervention (FFPE bulk or cryo tissue)
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- Patients have received radiotherapy and alkylating chemotherapy
- Patients are at least six months off radiotherapy and at least 4 weeks off chemotherapy prior to screening MRI prior to baseline
- Patients must be candidates for complete or partial on-trial resection and the on- trial resection must be postponable for six weeks
- Patients should be immunocompetent (i.e. no concomitant treatment with dexamethasone (or equivalent), or receive stable/decreasing steroid levels not exceeding 2 mg/day dexamethasone (or equivalent) during the last 3 days prior to baseline)
- Karnofsky Performance Status ≥ 70
- Adequate bone marrow function:
- absolute neutrophil counts (ANC) ≥ 1.5 x 109/L,
- hemoglobin ≥ 9 g/dL,
- platelets ≥ 100 x 109/L
- Adequate renal function: serum creatinine ≤ 2.0 x ULN, or creatine clearance > 30 mL/min
- Adequate hepatic function:
- Total bilirubin ≤ 1.5 × ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin ≥1.5 × ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at or below ULN.
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN.
- Postmenopausal or evidence of non-childbearing status. For women of childbearing potential negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at baseline as well as highly effective forms of contraception have to be in place thereafter.
- Female patients of childbearing potential and male patients with partners of childbearing potential who are sexually active must agree to the use of two forms of contraception in combination (male condom and one highly effective method). These should be started immediately after signing the informed consent form and continued throughout the period of study treatment plus 6 months after EOT.
Who cannot join
- Presence of 1p19q co-deletion (Per local assessment, q)
- Patient is unable to swallow oral medication
- Patient is unlikely to cooperate in the study
- Known hypersensitivity to any of the components of vorasidenib
- Known hypersensitivity to any of the components of the IDH1 vaccine (IDH1-vac)
- Ongoing use of medications that are CYP2C8, CYP2C9, CYP2C19, or CYP3A substrates with a narrow therapeutic index.
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- Relevant lactose intolerance
- Any prior treatment with vorasidenib or any other IDH inhibitor
- Any prior treatment with IDH1-vac
- Pregnancy and lactation
- Current participation in another interventional study or participation in other clinical trials or their observation period during the last 30 days before the first administration of the IMP(s).participation in non-interventional registries or epidemiological studies is allowed
- Have received prior systemic anticancer therapy (other than surgery) within 4 weeks (or 6 weeks for nitrosoureas) of the start of study treatment. In addition, the first dose of study treatment should not occur before a period of 28 days or ≥5 half-lives of any prior investigational agent have elapsed, whichever is longer
- Any use of immunosuppressive medication until 4 weeks prior to baseline, except for the following:
- intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
- Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Patients with history or presence of HIV and/or HBV/HCV positivity (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
- Active infection requiring systemic therapy.
- Patients who have received a live, attenuated vaccine within 4 weeks prior to the first administration of the study drug(s)
- Clinically significant (i.e., active) cardiovascular disease: Cerebral vascular accident/stroke (< 6 months prior to baseline), myocardial infarction (< 6 months prior to baseline), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Have a heart-rate corrected QT interval using the formula of Bazett or other factors that increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with bundle branch block and prolonged QTcF are permitted with approval of the Medical Monitor.
- Have features assessed as high-risk by the Investigator, including brainstem involvement either as primary location or by tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor in the opinion of the Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with activities of daily life AND failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen).
- Concurrent active malignancy except for a) curatively resected nonmelanoma skin cancer or b) curatively treated carcinoma in situ. Subjects with previously treated malignancies are eligible provided they have been disease-free for 3 years at Baseline
- Have LVEF <40% by echocardiogram (ECHO) (or by other methods according to institutional practice) obtained within 28 days before the start of study treatment.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
NCT Heidelberg - Clinical Trial Center Trial Management and Support contact
About this study
The study aims to investigate the combination of the IDH1R132H peptide vaccine and the dual IDH1/2 inhibitor vorasidenib in patients with recurrent and/or progressive astrocytoma, WHO grade 2,3 and 4. The trial will assess the safety, and immunogenicity of the combined treatment.
Read the detailed description
Current standard of care for malignant gliomas, which includes surgery, radiotherapy, and alkylating chemotherapy, remains insufficient, as outcomes are still poor regardless of molecular markers. The INDIGO phase 3 trial demonstrated that vorasidenib significantly prolonged progression-free survival in patients with IDH-mutated gliomas grade 2 after surgery. Additionally, the NOA16 phase 1 trial highlighted the safety and immunogenicity of the mutant IDH1 vaccine (MIDH1-vac) in newly-diagnosed grade 3 and 4 astrocytomas, showing biological activity and favorable clinical outcomes when integrated into standard care. In addition, in the AMPLIFY-NEOVAC trial MIDH1-vac alone or in combination with Avelumab was investigated. The overall toxicity profile was acceptable. MIDH1-vac-induced immune responses were observed in the majority of patients. These findings, along with evidence that IDH inhibition can enhance immune activation, provide a strong rationale for exploring the synergy between vaccination and mutant IDH inhibition.
- Being tested
- IDH1R132H-vac, Vorasidenib 40 mg Oral Tablet, Aldara - Imiquimod 5%
- Keywords
- safety, immunogenicity, IDH1-vac, astrocytoma, phase 1, Vorasidenib
- Medical subject headings
- Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IDH1R132H-vacBiological
IDH1 peptide vaccine
Vorasidenib 40 mg Oral TabletDrug
Also called Voranigo
IDH1/2 Inhibitor
Aldara - Imiquimod 5%Drug
Imiquimod
| Study group | Role | What they receive |
|---|---|---|
| Safety Lead-in | Experimental | 300 µg peptide in 1.0 ml s.c. every 2 weeks, topical immunomodulator, 40 mg daily (may reduced to 20 mg daily) Receives: Biological: IDH1R132H-vac; Drug: Vorasidenib 40 mg Oral Tablet; Drug: Aldara - Imiquimod 5% |
| Main Therapy, Primary Treatment - Arm 1 | Experimental | 300 µg peptide in 1.0 ml s.c. every 2 weeks, topical immunomodulator Receives: Biological: IDH1R132H-vac; Drug: Aldara - Imiquimod 5% |
| Main Therapy, Primary Treatment - Arm 2 | Experimental | 300 µg peptide in 1.0 ml s.c. every 2 weeks, topical immunomodulator, 40 mg daily (may reduced to 20 mg daily) Receives: Biological: IDH1R132H-vac; Drug: Vorasidenib 40 mg Oral Tablet; Drug: Aldara - Imiquimod 5% |
| Main Therapy, Primary Treatment - Arm 3 | No intervention | No Intervention |
| Main Therapy, Secondary Treatment | Experimental | 300 µg peptide in 1.0 ml s.c. 3 x every 12 weeks afterwards every 24 weeks , topical immunomodulator, 40 mg daily (may reduced to 20 mg daily) Receives: Biological: IDH1R132H-vac; Drug: Vorasidenib 40 mg Oral Tablet; Drug: Aldara - Imiquimod 5% |
What is being measured
The primary outcome is the main question the study is designed to answer.
regime-limiting toxicity (RLT)
- any injection site reaction of CTCAE grade 4
- any injection site reaction of CTCAE grade 3 that persists after two weeks
- any transaminase elevation of CTCAE grade 4
- any grade 3 AE that is related to the treatment regime except for
- nausea
- vomiting, who have not received optimal treatment with antiemetics
- diarrhea, who have not received optimal treatment with antidiarrheas
- fatigue
- edema cerebral of CTCAE grade 4
- death except for death due to disease progression
Measured: safety lead-in: week 1 to 13 main therapy: week 1 to 37
Secondary outcomes (4)
Immunogenicity
Immunogenicity, defined as presence of IDH1R132H-specific T-cells and/or antibody Responses in the peripheral circulation (all Arms) and/or the presence of IDH1R132H-specific T-cells in the tumor tissue (Arm 1, 2 only)
Measured: through study completion, an average of 3 years
Overall Survival
Overall survival (OS)
Measured: through study completion, an average of 3 years
Progression-free survival
Progression-free survival (PFS) according to RANO 2.0
Measured: through study completion, an average of 3 years
Overall response rate
Overall response rate (ORR) Response is defined as stable disease, partial response, complete response according to RANO 2.0.
Measured: through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2026
- Study start1 Jan 2027 (estimated)
- Primary completion31 Dec 2032 (estimated)
- Study completion31 Dec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent IDH1R132H-mutant Astrocytoma, Grade 2 - 4Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- The first part of the trial is "sequential", starting with the treatment dose of Vorasidenib and de-escalating based on a BOIN design. The second part of the trial is "factorial" randomized in three groups (1. IDH1-vac, 2. IDH1-vac + Vorasidenib and 3. no treatment).
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- Servier Affaires Médicales
- Responsible party
- Principal investigator, Michael Platten, Heidelberg University
- Investigators
- Michael Platten, Prof. Dr. med., Study chair, Department of Neurology | University Hospital Heidelberg - UK Mannheim Ltd. | Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07877415
- Sponsor's protocol ID
- UHD-iVOCAL
- Other IDs
- 2026-526504-73-00
- Acronym
- iVOCAL
- Status last verified
- Oct 2026
- First submitted
- 21 Jul 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No