Trial Outcomes & Findings for HIF-2 Alpha Inhibitor PT2385 in Treating Patients With Recurrent Glioblastoma (NCT NCT03216499)

Last Updated: 2022-05-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2022-05-09

Participant Flow

Enrollment Sept 14, 2017 - March 9, 2018, all glioblastoma multiforme (GBM) patients

Participant milestones

Participant milestones
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) Patients receive hypoxia inducible factor (HIF)-2 alpha inhibitor PT2385 per os (PO) twice daily (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 HIF-2 alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) n=24 Participants 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 HIF-2alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Age, Continuous	62.1 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
MGMT Promoter Status Methylated	11 Participants n=5 Participants
MGMT Promoter Status Not Methylated	12 Participants n=5 Participants
MGMT Promoter Status Indeterminate	1 Participants n=5 Participants
Extent of tumor resection Biopsy	2 Participants n=5 Participants
Extent of tumor resection Subtotal resection	8 Participants n=5 Participants
Extent of tumor resection Gross total resection	14 Participants n=5 Participants
Karnofsky Performance Status Score	80 score on a scale n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Outcome measures

Outcome measures
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) n=24 Participants 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 HIF-2alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Tumor Radiographic Response as Assessed by the RANO Criteria complete response	0 Participants
Tumor Radiographic Response as Assessed by the RANO Criteria partial response	0 Participants
Tumor Radiographic Response as Assessed by the RANO Criteria stable	7 Participants
Tumor Radiographic Response as Assessed by the RANO Criteria progression	17 Participants

SECONDARY outcome

Timeframe: Assessed up to 2 years

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.

Outcome measures

Outcome measures
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) n=24 Participants 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 HIF-2alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Progression-free Survival (PFS)	1.8 months Interval 1.6 to 2.5

SECONDARY outcome

Timeframe: 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

Overall survival (in months) will be estimated using Kaplan-Meier method along with 95% confidence interval.

Outcome measures

Outcome measures
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) n=24 Participants 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 HIF-2alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Overall Survival	7.7 months Interval 4.9 to 12.6

SECONDARY outcome

Timeframe: Up to 1 year

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.

Outcome measures

Outcome measures
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) n=24 Participants 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 HIF-2alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Incidence of Grade 3 and Grade 4 Adverse Events grade 3 anemia	1 Participants
Incidence of Grade 3 and Grade 4 Adverse Events grade 3 Hyperglycemia	1 Participants
Incidence of Grade 3 and Grade 4 Adverse Events grade 3 hyponatremia	2 Participants
Incidence of Grade 3 and Grade 4 Adverse Events grade 3 Hypoxia	2 Participants
Incidence of Grade 3 and Grade 4 Adverse Events grade 4 Hypoxia	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 15 cycle 1

Minimum concentration (Cmin) on Day 15 of cycle 1. * Cycle 1, Week 1, Day 1, Pre-dose 1: within 15 minutes prior to dose * Cycle 1, Week 1, Day 1, 6 Hours Post-dose 1: 6 hours +/- 15 minutes post-dose * Cycle 1, Week 3, Day 15, Pre-dose 1: within 30 minutes prior to dose

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 15 cycle 1

Drug exposure levels in 3 groups: Cmin \>1000ng/mL; Cmin: 300-1000 ng/mL and Cmin \<300ng/mL

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At baseline

Baseline Tumor acidity was measured using pH-weighted amine chemical exchange saturation transfer (CEST) MRI contrast on the Magnetic Resonance Imaging R\^2 = "reversible transverse relaxation rate" (and is proportional to oxygen extraction and thus hypoxia). MTR = MTRasym "the asymmetry in the magnetization transfer ratio at 3ppm from water" (and it is a surrogate of tumor acidity (MTR) pH quantitative measure of the acidity or basicity (pH) of aqueous or other liquid solutions. Lower pH values correspond to solutions which are more acidic in nature, while higher values correspond to solutions which are more basic or alkaline. Exp = exposure Acid = Acidity Perit Tiss = Peritumoral Tissue Enh Tum = Enhancing Tumor DurTx = Duration treatment

Outcome measures

Outcome data not reported

Adverse Events

Treatment (HIF-2 Alpha Inhibitor PT2385)

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) n=24 participants at risk 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 HIF-2alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Respiratory, thoracic and mediastinal disorders Hypoxia	8.3% 2/24 • Number of events 3 • Approximately 1 year
Blood and lymphatic system disorders Anemia	4.2% 1/24 • Number of events 1 • Approximately 1 year
Metabolism and nutrition disorders Hyponatremia	8.3% 2/24 • Number of events 2 • Approximately 1 year
Metabolism and nutrition disorders Hyperglycemia	4.2% 1/24 • Number of events 1 • Approximately 1 year

Other adverse events

Other adverse events
Measure	Treatment (HIF-2 Alpha Inhibitor PT2385) n=24 participants at risk 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 HIF-2alpha Inhibitor PT2385: Given PO Pharmacological Study: Correlative studies Laboratory Biomarker Analysis: Correlative studies Pharmacogenomic Study: Correlative studies
Blood and lymphatic system disorders aniema	45.8% 11/24 • Number of events 30 • Approximately 1 year
Psychiatric disorders confusion	16.7% 4/24 • Number of events 4 • Approximately 1 year
Nervous system disorders Dysphasia	8.3% 2/24 • Number of events 2 • Approximately 1 year
General disorders Edema Limbs	8.3% 2/24 • Number of events 2 • Approximately 1 year
General disorders Fatigue	29.2% 7/24 • Number of events 7 • Approximately 1 year
Metabolism and nutrition disorders Hyponatremia	8.3% 2/24 • Number of events 4 • Approximately 1 year
Metabolism and nutrition disorders Hypophosphatemia	25.0% 6/24 • Number of events 6 • Approximately 1 year
Investigations lymphocyte decrease	8.3% 2/24 • Number of events 6 • Approximately 1 year
Nervous system disorders muscle weakness	16.7% 4/24 • Number of events 6 • Approximately 1 year
Gastrointestinal disorders Nausea	20.8% 5/24 • Number of events 5 • Approximately 1 year
Investigations platelet count decrease	16.7% 4/24 • Number of events 6 • Approximately 1 year

Additional Information

Roy Strowd, MD

Adult Brain Tumor Consortium (ABTC)

Phone: 410-955-8837

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place