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A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02974738
Recruitment Status : Active, not recruiting
First Posted : November 28, 2016
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Peloton Therapeutics, Inc.

Brief Summary:
The primary objective of this study is to identify the maximum tolerated dose (MTD) of PT2977 Tablets and/or the recommended Phase 2 dose (RP2D) of PT2977 Tablets in patients with advanced solid tumors

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Solid Tumor Solid Carcinoma Solid Tumor, Adult ccRCC RCC, Clear Cell Adenocarcinoma RCC Kidney Cancer Clear Cell Renal Cell Carcinoma Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma Recurrent Renal Cell Carcinoma, Clear Cell Adenocarcinoma Glioblastoma Glioblastoma, Adult GBM Glioblastoma Multiforme Drug: PT2977 Phase 1

Detailed Description:

Part 1A: This is a Phase 1, multiple-dose, dose-escalation trial of PT2977 Tablets, where patients with advanced solid tumors will be assigned to sequential dose cohorts. Patient safety will be monitored with frequent physical examinations, vital sign measurements, electrocardiograms (ECGs), and hematology and chemistry laboratory studies, and by recording all adverse events (AEs). Blood will be obtained for analysis of the concentration of PT2977 and to assess biomarkers.

Part 1B: Once the MTD and/or the RP2D is achieved, and expansion cohort of 25 patients with advanced clear cell renal cell carcinoma (ccRCC) will be enrolled.

Part 2: After determination of the MTD/RP2D, up to 25 patients with other specified solid tumors may be enrolled. Up to 3 different tumor types may be included in this part of the study.

Part 2A: A cohort of 25 patients with glioblastoma (GBM)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multiple-Dose, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors
Study Start Date : December 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Part 1A

Drug: PART 1A: PT2977 for the treatment of advanced solid tumors

PT2977 inhibits HIF-2α and is a novel approach to treatment of solid tumors.

Drug: PT2977
PT2977 is a highly selective small molecule that inhibits the function of the HIF-2α transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis
Other Name: PT2977 Tablets, PT-2977, HIF-2α inhibitor

Experimental: Part 1B

Drug: PART 1B: PT2977 for the treatment of advanced ccRCC

PT2977 inhibits HIF-2α and is a novel approach to treatment of ccRCC.

Drug: PT2977
PT2977 is a highly selective small molecule that inhibits the function of the HIF-2α transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis
Other Name: PT2977 Tablets, PT-2977, HIF-2α inhibitor

Experimental: Part 2

Drug: Part 2: PT2977 for the treatment of other specified solid tumors

PT2977 inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.

Drug: PT2977
PT2977 is a highly selective small molecule that inhibits the function of the HIF-2α transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis
Other Name: PT2977 Tablets, PT-2977, HIF-2α inhibitor

Experimental: Part 2A

Drug: Part 2A: PT2977 for the treatment of patients with recurrent GBM who have been previously treated with radiation therapy and temozolomide

PT2977 inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.

Drug: PT2977
PT2977 is a highly selective small molecule that inhibits the function of the HIF-2α transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis
Other Name: PT2977 Tablets, PT-2977, HIF-2α inhibitor




Primary Outcome Measures :
  1. maximum tolerated dose (MTD) [ Time Frame: 3 Weeks ]
    21-Day Dose Limiting Toxicity Observation Period per Dose Group



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a diagnosis of locally advanced or metastatic solid tumor
  • Is of age ≥ 18 years
  • Has a life expectancy of ≥ 6 months
  • Has adequate organ function
  • If a female patient, must be surgically sterile, post-menopausal, or must agree to use physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration, or if a male patient with a female partner, must agree to use physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration
  • Able to swallow oral medications

Additional Inclusion Criteria for GBM cohort

  • Must have histologically confirmed glioblastoma, IDH-wild type that is first recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria
  • Must have archival tumor tissue available from a previous surgery for glioblastoma
  • Must have measurable (defined as at least 1 cm x 1 cm) contrast-enhancing lesion by MRI imaging within 21 days of starting treatment
  • 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

Exclusion Criteria:

  • Has a history of untreated brain metastasis or history of leptomeningeal disease or spinal cord compression
  • Has failed to recover from the reversible effects of prior anticancer therapy
  • Has uncontrolled or poorly controlled hypertension
  • Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease
  • Has had any major cardiovascular event within 6 months prior to study drug administration
  • Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
  • Has had major surgery within 4 weeks before first study drug administration
  • Has known HIV
  • Has an active infection requiring systemic treatment
  • Is participating in another therapeutic clinical trial

Additional Excusion Criteria for GBM cohort:

  • Has received prior anti-VEGF therapy including bevacizumab (i.e. patients must be bevacizumab naïve)
  • Is receiving enzyme-inducing anti-epileptic drugs (EIAED). 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 PT2977

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02974738


Locations
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United States, Florida
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, North Carolina
Wake Forest Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Peloton Therapeutics, Inc.

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Responsible Party: Peloton Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02974738     History of Changes
Other Study ID Numbers: PT2977-101
First Posted: November 28, 2016    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Carcinoma
Adenocarcinoma
Glioblastoma
Carcinoma, Renal Cell
Adenocarcinoma, Clear Cell
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases