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TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04770246
Recruitment Status : Active, not recruiting
First Posted : February 25, 2021
Last Update Posted : November 14, 2022
Sponsor:
Information provided by (Responsible Party):
Taiho Oncology, Inc.

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of TAS-117 in patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations Drug: TAS-117 Phase 2

Detailed Description:

Study TAS-117-201 is an open-label, single-arm Phase 2 study evaluating the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of TAS-117 in patients with advanced or metastatic solid tumors harboring germline PTEN inactivating mutations. The study will be conducted in two parts:

  • Part A: Safety lead-in (Dose Escalation and Dose Regimen Confirmation)
  • Part B: Single-arm Phase 2 study

Patients will receive TAS-117 orally every day or intermittently on a 21-day cycle

  • Part A (Dose Escalation): up to 36 adult patients with advanced or metastatic solid tumors (excluding primary brain tumors) irrespective of gene alterations. The Dose Escalation consists of 2 cohorts: Daily Dose Regimen and Intermittent Dose Regimen.
  • Part A (Dose Regimen Confirmation): approximately 6 adult or adolescent patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations
  • Part B (Phase 2): approximately 54 adult or adolescent patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations

Treatment will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment discontinuation is met. For patients who discontinue treatment for reasons other than disease progression, tumor assessments should be continued until radiologic disease progression is documented or until initiation of subsequent new anticancer therapy (whichever occurs first).

Patients will be followed for survival every 12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated early by the Sponsor.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations
Actual Study Start Date : March 31, 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : December 2024

Arm Intervention/treatment
Experimental: TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in)
Advanced or metastatic solid tumors irrespective of gene alterations
Drug: TAS-117
TAS-117 will be dosed orally every day on a 21-day cycle

Experimental: TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in)
Advanced or metastatic solid tumors irrespective of gene alterations
Drug: TAS-117
TAS-117 will be dosed intermittently on a 21-day cycle

Experimental: TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in)
Advanced or metastatic solid tumors with germline PTEN inactivating mutations
Drug: TAS-117
TAS-117 will be dosed orally every day or intermittently on a 21-day cycle

Experimental: TAS-117 Phase 2 (Part B)
Advanced or metastatic solid tumors with germline PTEN inactivating mutations
Drug: TAS-117
TAS-117 will be dosed orally every day or intermittently on a 21-day cycle




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events and dose-limiting toxicities (safety and tolerability) and MTD of TAS-117 in Part A [ Time Frame: 21 days for DLT evaluation, approximately 7 months for the others ]
    Number of patients with abnormal laboratory values, treatment emergent AEs, abnormal vital signs and ECG, and Dose-limiting toxicities (DLTs)

  2. Recommended Phase 2 Dose (RP2D) of TAS-117 in Part A [ Time Frame: 21 days for DLT evaluation, approximately 7 months for the others ]
  3. Objective Response Rate (ORR) in Part B (including all patients with germline PTEN mutations in Part A) [ Time Frame: Approximately 6 months ]
    ORR, defined as the proportion of patients experiencing a best overall response of CR or PR per RECIST 1.1.


Secondary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (safety) in Part B [ Time Frame: Approximately 7 months ]
    Number of patients with abnormal laboratory values, treatment-emergent AEs, abnormal vital signs and ECG

  2. Disease Control Rate (DCR) [ Time Frame: Approximately 6 months ]
    DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR).

  3. Duration of Response (DOR) [ Time Frame: Approximately 6 months ]
    DOR, defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

  4. Progression Free Survival (PFS) [ Time Frame: Approximately 6 months ]
    PFS, defined as the time from date of the first dose of study treatment to the date of disease progression based on Investigator assessment of radiographic images or death, whichever occurs first.

  5. Overall Survival (OS) [ Time Frame: Approximately 12 months ]
    OS, defined as the time from the date of first dose to the death date.

  6. Pharmacokinetics (PK) profile of TAS-117 in Part A [ Time Frame: 21 days ]
    maximum plasma concentration (Cmax)

  7. Pharmacokinetics (PK) profile of TAS-117 in Part A [ Time Frame: 21 days ]
    area under the plasma concentration-time curve (AUC)

  8. Pharmacokinetics (PK) profile of TAS-117 in Part A [ Time Frame: 21 days ]
    time to reach maximum plasma concentration (Tmax)

  9. Pharmacokinetics (PK) profile of TAS-117 in Part A [ Time Frame: 21 days ]
    terminal elimination half-life (T1/2)

  10. Pharmacodynamics (PD) profile of TAS-117 in Part A [ Time Frame: 21 days ]
    Evaluate Total and Phosphorylated AKT and PRAS40



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  2. Dose Escalation in Part A

    1. ≥18 years of age.
    2. Histologically or cytologically confirmed advanced or metastatic solid tumors
    3. Has progressed after standard treatment for advanced or metastatic disease or was intolerant to or ineligible for available standard therapies.
    4. Patients with solid tumors irrespective of gene alterations.
    5. Patients with at least one measurable or non-measurable lesion per RECIST1.1
  3. Dose and Regimen Confirmation in Part A and Phase 2 (Part B)

    1. ≥12 years of age. Patients age ≥12 and <18 years must have a body weight of ≥40 kg.
    2. Histologically confirmed advanced or metastatic solid tumors.
    3. Has progressed after standard treatment for advanced or metastatic disease or was intolerant or ineligible to available standard therapies.
    4. Patients with locally confirmed germline PTEN inactivating mutations determined from a blood sample.
    5. Patients with at least one measurable lesion per RECIST 1.1.

Exclusion Criteria

  1. History or current evidence of interstitial lung disease that requires steroid medication.
  2. Current evidence of diabetes mellitus that requires insulin therapy.
  3. Prior treatment with PI3K/AKT/mTOR pathway inhibitors.
  4. Patients with primary brain tumor.
  5. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastasis.
  6. Currently receiving chronic corticosteroid therapy of ≥10 mg/day of prednisone or its equivalent.

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): NCT04770246


Locations
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United States, California
Sarcoma Oncology Research Center
Santa Monica, California, United States, 90403
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Cleveland Clinic Lerner Research Institute
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Austria
Medical University of Vienna
Vienna, Austria, 1090
France
Institut Gustave Roussy
Villejuif, Ile De France, France, 98405
United Kingdom
Sarah Cannon Research Institute
London, United Kingdom, W1G 6AD
Sponsors and Collaborators
Taiho Oncology, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Taiho Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04770246    
Other Study ID Numbers: TAS-117-201
2020-004770-22 ( EudraCT Number )
First Posted: February 25, 2021    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Taiho Oncology, Inc.:
TAS-117
AKT inhibitor
Allosteric inhibitor
Advanced solid tumor
Metastatic solid tumor
PTEN
Germline PTEN
Inactivating mutation
Adolescent patients
Adult patients
Additional relevant MeSH terms:
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Neoplasms