Trial of IDH305 in IDH1 Mutant Grade II or III Glioma

NCT02977689 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 16-00589
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioma

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

Outcome Measures

Primary Outcomes (1)

• Radiographic response rate

  up to 8 weeks

Secondary Outcomes (6)

• Safety (adverse events) of the protocol therapy

  up to 2 years

• Volumetric radiographic response rate

  up to 6 months

• Median duration of response

  up to 6 months

• Median progression-free survival (PFS)

  up to 6 months

• Progression-free survival at 6 months (PFS6)

  up to 6 months

Study Arms (1)

IDH305

EXPERIMENTAL

IDH305 550 mg, oral, two times per day

Drug: IDH305

Interventions

IDH305 DRUG

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

IDH305

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• NYU Langone Health: lead
• Novartis: collaborator

Study Sites (1)

Laura & Isaac Perlmutter Cancer Center & NYU Langone Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma; Oligodendroglioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Andrew S Chi, MD, PhD

  NYU Perlmutter Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: November 30, 2016
• Study Start: April 1, 2018
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: December 20, 2017

Record last verified: 2017-12

Locations

US (1)