HIF-2 Alpha Inhibitor PT2385 in Treating Patients With Recurrent Glioblastoma

NCT03216499 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: ABTC 1602IRB00132128UM1CA137443
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 10

Brief Summary

This phase II trial studies how well HIF-2 alpha inhibitor PT2385 works in treating patients with recurrent glioblastoma. HIF-2 alpha inhibitor PT2385 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Tumor Radiographic Response as Assessed by the RANO Criteria

  Tumor radiographic response assessed by Response Assessment in Neuro-Oncology (RANO) criteria. * Complete Response (CR) = no change in size of T1-gadolinium-enhancing (T1-Gd+) disease, stable or reduced T2/FLAIR signal, no new lesion, no corticosteroid use, and stable or improved clinical status * Partial Response (PR) = ≥50% change in size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status * Stable Disease (SD) = \<50% reduction to \<25% increase size of T1-Gd+ disease, stable or reduced T2/FLAIR signal, no new lesion, stable or reduced corticosteroid use, and stable or improved clinical status * Progressive Disease (PD) = ≥25% increase size of T1-Gd+ disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status.

  Up to 2 years

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  Assessed up to 2 years

• Overall Survival

  From the date of treatment start to the date of death occurrence/or censored at the time of last known alive, assessed up to 2 years

• Incidence of Grade 3 and Grade 4 Adverse Events

  Up to 1 year

Other Outcomes (3)

• Pharmacokinetics (Cmin) for PT2385

  Day 15 cycle 1

• Pharmacokinetics for PT2385 Drug Exposure

  Day 15 cycle 1

• Determine Association Between Baseline Tumor Acidity and PT2385 (Imaging)

  At baseline

Study Arms (1)

Treatment (HIF-2 alpha inhibitor PT2385)

EXPERIMENTAL

Patients receive HIF-2 alpha inhibitor PT2385 PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Pharmacological Study Laboratory Biomarker Analysis Pharmacogenomic Study

Drug: HIF-2alpha Inhibitor PT2385; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study

Interventions

HIF-2alpha Inhibitor PT2385 DRUG

Given PO

Also known as: HIF-2alpha Inhibitor PT2385, PT2385

Treatment (HIF-2 alpha inhibitor PT2385)

Pharmacological Study OTHER

Correlative studies

Treatment (HIF-2 alpha inhibitor PT2385)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (HIF-2 alpha inhibitor PT2385)

Pharmacogenomic Study OTHER

Correlative studies

Also known as: PHARMACOGENOMIC, Pharmacogenomic Study

Treatment (HIF-2 alpha inhibitor PT2385)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed glioblastoma that is progressive or recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria with:
• New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids
• Increase by \>= 25% in the sum of the products of perpendicular diameters between the postradiotherapy scan with the smallest tumor measurement and a scan at least 12 weeks from completion of radiation therapy (RT) + temozolomide (TMZ), on stable or increasing doses of corticosteroids
• \*\* Note: clinical deterioration not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment but not for entry onto a clinical trial for recurrence
• Tumor O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction, (MSPCR), or quantitative polymerase chain reaction (PCR)) are acceptable
• Patients must have a tumor tissue form indicating availability of archived tissue from a previous surgery for glioblastoma, completed and signed by a pathologist
• Patients must have measurable (defined by at least 1 cm x 1 cm) contrast-enhancing disease by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment
• Patients must be able to undergo MRI of the brain with gadolinium; patients must be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days) prior to this baseline MRI
• Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide
• Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not Food and Drug Administration (FDA)-approved) agents
• weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)

You may not qualify if:

• Patients receiving any other investigational agents are ineligible
• Patients must not have received prior anti- Vascular endothelial growth factor (VEGF) therapy including bevacizumab (i.e. patients must be bevacizumab naive)
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PT2385 are ineligible
• Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of PT2385
• Patients with a history of bleeding diathesis are ineligible
• Patients who have not recovered to \< Common Terminology Criteria for Adverse Events (CTCAE) grade 2 toxicities related to prior therapy are ineligible
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PT2385
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible due to potential drug-drug interactions with PT2385

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator
• Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): collaborator

Study Sites (10)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410, United States

Location

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Abrams Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Strowd R, Ellingson B, Raymond C, Yao J, Wen PY, Ahluwalia M, Piotrowski A, Desai A, Clarke JL, Lieberman FS, Desideri S, Nabors LB, Ye X, Grossman S. Activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrence of glioblastoma. J Neurooncol. 2023 Oct;165(1):101-112. doi: 10.1007/s11060-023-04456-7. Epub 2023 Oct 21.

  PMID: 37864646 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

PT2385; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Results Point of Contact

• Title: Roy Strowd, MD
• Organization: Adult Brain Tumor Consortium (ABTC)

jfisher@jhmi.edu

410-955-8837

Study Officials

• Roy Strowd, MD

  Wake Forest /ABTC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: July 11, 2017
• First Posted: July 13, 2017
• Study Start: September 14, 2017
• Primary Completion: August 31, 2019
• Study Completion: June 5, 2020
• Last Updated: May 9, 2022
• Results First Posted: September 21, 2020

Record last verified: 2022-01

Locations

US (10)