Recurrent GlioblastomaPhase 2PT2385NCT03216499
HIF-2 Alpha Inhibitor PT2385 in Treating Patients With Recurrent Glioblastoma
A Phase 2 study testing HIF-2alpha Inhibitor PT2385, Pharmacological Study and Laboratory Biomarker Analysis in people with Recurrent Glioblastoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioblastoma
- What is being tested?
- HIF-2alpha Inhibitor PT2385, Pharmacological Study and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 10 sitesUnited States
- Study dates
- 14 Sep 2017to 5 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- • 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
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- 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:
- 12 weeks from the completion of radiation
- 6 weeks from a nitrosourea chemotherapy
- 3 weeks from a non-nitrosourea chemotherapy
- 4 weeks from any investigational (not Food and Drug Administration (FDA)-approved) agents
- 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
- Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
- Absolute neutrophil count >= 1,500/microliter (mcL)
- Platelets >= 100,000/mcL
- Hemoglobin >= 9 g/dL
- Total bilirubin =< institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT))/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =< 4 x institutional upper limit of normal
- Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73m^2 for patients with creatinine levels above institutional normal
- Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
- Patients must be able to provide written informed consent
- Women of childbearing potential must have a negative serum pregnancy test prior to study start; women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug
- Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
- Patients must be able to swallow tablets
Who cannot join
- • 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
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- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35294-3410
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, 90095
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Abrams Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Single-Arm, Open-Label Phase II Efficacy Study of First-in-Class HIF-2 Alpha Inhibitor, PT2385, for Patients With Recurrent Glioblastoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the efficacy of hypoxia inducible factor (HIF)-2 alpha inhibitor PT2385 (PT2385) as measured by radiographic response rate (by Response Assessment in Neuro-Oncology, RANO, criteria) in patients with recurrent glioblastoma.
SECONDARY OBJECTIVES:
- To estimate the efficacy of PT2385 as measured by progression free and overall survival in patients with recurrent glioblastoma.
II. To determine the safety of oral PT2385 in patients with recurrent glioblastoma.
TERTIARY OBJECTIVES:
- To describe the pharmacokinetic and pharmacodynamic properties of PT2385 in patients with recurrent glioblastoma.
II. To describe baseline intratumoral hypoxia using novel, advanced magnetic resonance (MR)-based neuroimaging sequences in patients with recurrent glioblastoma.
III. To explore genetic polymorphisms involved in the metabolism of PT2385.
OUTLINE:
Patients receive HIF-2 alpha inhibitor PT2385 orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for 2 years and every 6 months thereafter.
- Conditions
- Recurrent Glioblastoma
- Being tested
- HIF-2alpha Inhibitor PT2385, Pharmacological Study, Laboratory Biomarker Analysis, Pharmacogenomic Study
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIF-2alpha Inhibitor PT2385Drug
Also called HIF-2alpha Inhibitor PT2385, PT2385
Given PO
Correlative studies
Laboratory Biomarker AnalysisOther
Correlative studies
Pharmacogenomic StudyOther
Also called PHARMACOGENOMIC, Pharmacogenomic Study
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: HIF-2alpha Inhibitor PT2385; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis; Other: Pharmacogenomic Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Secondary outcomes (3)
Progression-free Survival (PFS)
PFS (in months) will be estimated using Kaplan-Meier method along with 95% confidence interval. Definition of PFS is date treatment started to the date of progression.
Measured: Assessed up to 2 years
Overall Survival
Overall survival (in months) will be estimated using Kaplan-Meier method along with 95% confidence interval.
Measured: 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
Number of participants experiencing grade 3 and grade 4 adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2017
- Study start14 Sep 2017
- Primary completion31 Aug 2019
- Study completion5 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent GlioblastomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Responsible party
- Sponsor
- Investigators
- Roy Strowd, MD, Study chair, Wake Forest /ABTC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03216499
- Sponsor's protocol ID
- ABTC 1602
- Other IDs
- IRB00132128, UM1CA137443
- Acronym
- PT2385
- Status last verified
- Jan 2022
- First submitted
- 11 Jul 2017
- Last updated
- 9 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37864646
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Arm, Open-Label Phase II Efficacy Study of First-in-Class HIF-2 Alpha Inhibitor, PT2385, for Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT03216499
- Acronym / sponsor ID
- PT2385 / ABTC 1602
- Conditions
- Recurrent Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Study start
- 14 Sep 2017 (actual)
- Primary completion
- 31 Aug 2019 (actual)
- Study completion
- 5 Jun 2020 (actual)
- First posted
- 13 Jul 2017 (actual)
- Results
- Posted 21 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the efficacy of hypoxia inducible factor (HIF)-2 alpha inhibitor PT2385 (PT2385) as measured by radiographic response rate (by Response Assessment in Neuro-Oncology, RANO, criteria) in patients with recurrent glioblastoma.
SECONDARY OBJECTIVES:
- To estimate the efficacy of PT2385 as measured by progression free and overall survival in patients with recurrent glioblastoma.
II. To determine the safety of oral PT2385 in patients with recurrent glioblastoma.
TERTIARY OBJECTIVES:
- To describe the pharmacokinetic and pharmacodynamic properties of PT2385 in patients with recurrent glioblastoma.
II. To describe baseline intratumoral hypoxia using novel, advanced magnetic resonance (MR)-based neuroimaging sequences in patients with recurrent glioblastoma.
III. To explore genetic polymorphisms involved in the metabolism of PT2385.
OUTLINE:
Patients receive HIF-2 alpha inhibitor PT2385 orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for 2 years and every 6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (HIF-2 alpha inhibitor PT2385) | Experimental | Drug: HIF-2alpha Inhibitor PT2385, Other: Pharmacological Study, Other: Laboratory Biomarker Analysis, Other: Pharmacogenomic StudyPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- • 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:
- 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
Key exclusion criteria (9 listed)
- • Patients receiving any other investigational agents are ineligible
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIF-2alpha Inhibitor PT2385Also: HIF-2alpha Inhibitor PT2385, PT2385Given PO | Drug | Treatment (HIF-2 alpha inhibitor PT2385) |
| Pharmacological StudyCorrelative studies | Other | Treatment (HIF-2 alpha inhibitor PT2385) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (HIF-2 alpha inhibitor PT2385) |
| Pharmacogenomic StudyAlso: PHARMACOGENOMIC, Pharmacogenomic StudyCorrelative studies | Other | Treatment (HIF-2 alpha inhibitor PT2385) |
Primary outcome
Tumor Radiographic Response as Assessed by the RANO Criteria
Time frame: Up to 2 years
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.
3 secondary outcomes
Progression-free Survival (PFS)
Time frame: Assessed up to 2 years
Overall Survival
Time frame: 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
Time frame: Up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37864646Strowd 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roy Strowd, MD study chair
Wake Forest /ABTC
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HIF-2alpha Inhibitor PT2385, Pharmacological Study and Laboratory Biomarker Analysis in people with Recurrent Glioblastoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 10 sites 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 27 inclusion and 9 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: finished, as of the sponsor's last update on 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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?
Yes. Results are posted in the registry (first posted 21 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tumor Radiographic Response as Assessed by the RANO Criteria (time frame: Up to 2 years). 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 NCT03216499, which also lists 1 linked publication.
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 9 May 2022; AzTrials last refreshed its copy on 6 Nov 2026.