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GliomaPhase 2NCT02977689

Trial of IDH305 in IDH1 Mutant Grade II or III Glioma

A Phase 2 study testing IDH305 in people with Glioma, run by NYU Langone Health at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to found out if the drug IDH305 is safe and effective in subjects with IDH1 mutant grade II or III glioma that has progressed after observation or radiation therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioma
What is being tested?
IDH305
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Apr 2018to Apr 2020
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements.
  • Subject must be ≥18 years of age.
  • Patients must have written documentation of IDH1 mutation at the R132 locus by immunohistochemistry or DNA sequencing in their tumor.
  • Histopathological diagnosis of a glioma of WHO grade II or III at initial diagnosis. Documentation of diagnosis by pathology report is sufficient for eligibility.
  • First line management with observation alone or external beam radiation after surgery. Notes or records from the treating oncologist or radiation oncologist are required for documentation of treatment history.
  • Patients must have unequivocal progression on brain MRI after observation or external beam radiation. If a patient was initially diagnosed with a non-enhancing tumor and the tumor develops new contrast-enhancement at progression, they will be excluded except for the following exceptions:
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  • Patients with tumors that were contrast-enhancing at initial diagnosis of grade II or III glioma will be allowed if their tumors are contrast-enhancing at progression as well.
  • If a patient with a grade II or III glioma has a tumor that develops new contrast-enhancement at progression, the enhancing portion of the progressive tumor must be biopsy proven WHO grade II or III at progression.
  • Measurable tumor of at least 1 cm x 1 cm in diameter by MRI. The measurable tumor may be contrast-enhancing or non-enhancing.
  • Interval of at least 12 weeks from the completion of any prior radiotherapy and registration. If patients have not passed an interval of at least 12 weeks, they may still be eligible if they meet one or more of the following criteria:
  • New areas of tumor outside the original radiotherapy fields as determined by the investigator, or
  • Histologic confirmation of tumor (as opposed to pseudo-progression or radiation necrosis) through biopsy or resection
  • Collection of an archival tumor block with a minimum of 1 cm2 surface area of viable tumor or at least 20 unstained 5 micron slides from the most recent surgery.
  • Karnofsky performance status (KPS) ≥60.
  • An interval of at least 2 weeks (to start of study agent) between prior surgical resection of glioma, or one week for stereotactic biopsy of glioma.
  • Adequate hematologic, hepatic, and renal function defined by absolute neutrophil count ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥ 75 x 109/L (may have been transfused), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN), total bilirubin > 1 x ULN, and serum creatinine >1.5 x ULN

Who cannot join

  • Glioblastoma (WHO grade IV) histopathology on any tumor sample
  • Leptomeningeal gliomatosis
  • Unable to tolerate a contrast-enhanced brain MRI or if MRI is contraindicated
  • Two weeks since any major surgery treatment (mediastinoscopy, insertion of a central venous access device and insertion of a feeding tube are not considered major surgery) prior to registration, with the exception of stereotactic biopsy for glioma, in which case an interval of 1 week until registration is allowed.
  • Patients who are currently receiving treatment with a prohibited medication or herbal remedy that cannot be discontinued at least one week prior to the start of treatment.
  • Narrow therapeutic index substrates of CYP3A, CYP2C9, CYP2C19, and CYP2C8
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  • Medications, herbs and supplements that are strong inhibitors and strong inducers of CYP3A
  • Other herbal preparations and supplements
  • Inhibitors of UGT1A1
  • Prior exposure to a therapy targeting IDH1, including targeted inhibitors of IDH1 and anti-IDH1 vaccines.
  • Prior treatment with any cytotoxic chemotherapy, including but not limited to temozolomide, lomustine, Nimustine Hydrochloride (ACNU), bis(chloroethyl) nitrosourea (BCNU), procarbazine, vincristine, carboplatin, irinotecan, Gliadel wafer, cyclophosphamide, etoposide, etc. Chemotherapy is associated with hypermutation phenotype at recurrence and therefore patients who have had prior treatment with these agents are excluded.
  • Rapidly progressing neurological symptoms related to underlying disease requiring increasing doses of corticosteroids. Steroid use for management of gliomas is allowed but the dose must be stable for at least 1 week preceding the baseline MRI/CT. If the corticosteroid dose is increased between the date of imaging and the initiation of study treatment, a new baseline MRI is required.
  • Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within the prior 2 years from the time of registration; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
  • Patients with corrected QT using the Fridericia correction (QTcF) > 470 msec, or other clinically significant, uncontrolled heart disease, including acute myocardial infarction or unstable angina < 3 months prior to the first dose of IDH305.
  • Any other medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures such as the presence of other clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic, infectious, psychiatric or neurological disease.
  • Patients with Gilbert's syndrome or other heritable diseases of bile processing.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 30 days after the use of the investigational medication. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient
  • Combination of any two of the following (a+b, a+c, or b+c):
  • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal, for example hormone vaginal ring or transdermal hormone contraception.
  • In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  • Sexually active males must use a condom during intercourse while taking the drug and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via semen.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Laura & Isaac Perlmutter Cancer Center & NYU Langone Medical Center

    New York, New York, 10016

Other trials in United States

About this study

Official title: Phase 2 Study of IDH305 in Subjects With IDH1 Mutant Grade II or III Glioma That Has Progressed After Observation or Radiation Therapy

The purpose of this study is to found out if the drug IDH305 is safe and effective in subjects with IDH1 mutant grade II or III glioma that has progressed after observation or radiation therapy.

Read the detailed description

IDH305 is an orally available, brain-penetrant, mutant-selective allosteric IDH1 inhibitor that blocks mutant IDH1-dependent production of 2-HG.

Conditions
Glioma
Being tested
IDH305
Keywords
Isocitrate dehydrogenase (IDH), R-2-Hydroxyglutarate (2-HG), Gene encoding UDP-glucuronosyltransferase (UGT1A1), Glioblastoma (GBM), IDH305, IDHR132 mutations, Astrocytoma, Oligodendroglioma, Oligoastrocytoma, IDH1 R132H, IDH1
Medical subject headings
Glioma, Glioblastoma, Astrocytoma, Oligodendroglioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IDH305Drug

    study drug used to inhibit IDH1 mutation in these tumors, resulting in anti-tumor activity.

Study groups in NCT02977689
Study groupRoleWhat they receive
IDH305ExperimentalIDH305 550 mg, oral, two times per day
Receives: Drug: IDH305

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Radiographic response rate

    Measured: up to 8 weeks

Secondary outcomes (6)

  1. Safety (adverse events) of the protocol therapy

    The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) 4.03

    Measured: up to 2 years

  2. Volumetric radiographic response rate

    Measured: up to 6 months

  3. Median duration of response

    Measured: up to 6 months

  4. Median progression-free survival (PFS)

    Measured: up to 6 months

  5. Progression-free survival at 6 months (PFS6)

    Measured: up to 6 months

  6. 2-year overall survival (OS)

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2016 (estimated)
  2. Study startApr 2018 (estimated)
  3. Primary completionApr 2020 (estimated)
  4. Study completionApr 2020 (estimated)

Why it stopped: Novartis paused all study start-up activities due to safety evaluation of IDH305 compound.

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02977689
Sponsor's protocol ID
16-00589
Status last verified
Dec 2017
First submitted
28 Nov 2016
Last updated
20 Dec 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IDH305 in people with Glioma, run by NYU Langone Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 20 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Radiographic response rate (time frame: up to 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02977689.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2017.

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