Phase 2 Study of IDH305 in Low Grade Gliomas

NCT02987010 | Withdrawn Phase 2 DMC

• 1 other identifier: STU 102016-038
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Cohort A - neoadjuvant administration of IDH305 at 550 mg BID for 6 weeks followed by surgical resection at 6 weeks. If there is no evidence of progressive disease at 6 weeks (clinical, radiographic or histopathologic exam), the patient will continue on IDH305 at 550 mg BID post-operatively for a maximum of 11 additional 28 day cycles. Subsequent assessment of disease will occur every 2 months starting in Cycle 2. Cohort B - patients who have inoperable tumors but measurable 2HG pre-treatment will be treated with IDH305 at 550 mg BID x 6 weeks. If there is adequate sustained knockdown of 2HG on MRS and disease is stable or improved, then the patient will continue on treatment for a maximum of 11 additional 28 day cycles.

Conditions

Glioma

Outcome Measures

Primary Outcomes (2)

• IDH305 treatment of 2HG

  Number of participants treated with IDH305 leads to sustained knockdown of 2HG by MR spectroscopy from Baseline.

  Twice a day for 6 weeks for a maximum of 11 additional 28 day cycles

• 2HG response to IDH305

  Number of participants with radiographic and clinical response to knockdown of 2HG by IDH305 compared to Baseline.

  Every 112 days, up to 365 days

Study Arms (2)

Cohort A

EXPERIMENTAL

Neoadjuvant administration of IDH305 at 550 mg BID for 6 weeks followed by surgical resection at 6 weeks. If there is no evidence of progressive disease at 6 weeks (clinical, radiographic or histopathologic exam), the patient will continue on IDH305 at 550 mg BID post-operatively for a maximum of 11 additional 28 day cycles. Subsequent assessment of disease will occur every 2 months starting in Cycle 2.

Drug: IDH305

Cohort B

EXPERIMENTAL

Patients who have inoperable tumors but measurable 2HG pre-treatment will be treated with IDH305 at 550 mg BID x 6 weeks. If there is adequate sustained knockdown of 2HG on MRS and disease is stable or improved, then the patient will continue on treatment for a maximum of 11 additional 28 day cycles.

Drug: IDH305

Interventions

IDH305 DRUG

Isocitrate Dehydrogenase 1 inhibitor

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Written informed consent prior to any screening procedures that are not part of standard of care.
• Age greater than or equal to 18 years.
• Male or female of any racial or ethnic origin.
• Measurable 2HG by MR Spectroscopy (above threshold of 1mM, established at UTSW).
• Karnofsky Performance Status \> 70%.
• Measurable disease per RANO criteria.
• Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of therapy. Subjects with reproductive potential are defined as one who is biologically capable of becoming pregnant. Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use two effective forms of contraception during the study and for 30 days (females and males) following the last dose of IDH305.

You may not qualify if:

• HG by MR Spectroscopy below 1 mM.
• 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.
• Patients who have out of range laboratory values defined as:
• Absolute neutrophil count (ANC) \<1.0 x 109/L
• Hemoglobin (Hgb) \<8 g/dL
• Platelets \<75 x 109/L
• Total bilirubin \> ULN
• AST or ALT \>3 x ULN
• Serum creatinine \>1.5 x ULN
• Karnofsky Performance Status \< 70%.
• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

MeSH Terms

Conditions

Glioma

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: December 8, 2016
• Study Start: January 1, 2017
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: October 11, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share