Advanced or Metastatic Solid Tumors Irrespective of Gene AlterationsPhase 1NCT04770246
TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations
A Phase 1 study testing TAS-117 in people with Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations and Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations, run by Taiho Oncology, Inc. at 8 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations, Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations
- What is being tested?
- TAS-117
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 31 Mar 2021to 6 Mar 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Dose Escalation in Part A
- ≥18 years of age.
- Histologically or cytologically confirmed advanced or metastatic solid tumors
- Has progressed after standard treatment for advanced or metastatic disease or was intolerant to or ineligible for available standard therapies.
- Patients with solid tumors irrespective of gene alterations.
Show all 13Show fewer
- Patients with at least one measurable or non-measurable lesion per RECIST1.1
- Dose and Regimen Confirmation in Part A and Phase 2 (Part B)
- ≥12 years of age. Patients age ≥12 and <18 years must have a body weight of ≥40 kg.
- Histologically confirmed advanced or metastatic solid tumors.
- Has progressed after standard treatment for advanced or metastatic disease or was intolerant or ineligible to available standard therapies.
- Patients with locally confirmed germline PTEN inactivating mutations determined from a blood sample.
- Patients with at least one measurable lesion per RECIST 1.1.
Who cannot join
- History or current evidence of interstitial lung disease that requires steroid medication.
- Current evidence of diabetes mellitus that requires insulin therapy.
- Prior treatment with PI3K/AKT/mTOR pathway inhibitors.
- Patients with primary brain tumor.
- Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastasis.
- Currently receiving chronic corticosteroid therapy of ≥10 mg/day of prednisone or its equivalent.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States5 sites
Cleveland Clinic Lerner Research Institute
Cleveland, Ohio, 44195
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Sarcoma Oncology Research Center
Santa Monica, California, 90403
About this study
Official title: A Phase 2 Study of TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations
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.
Read the 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.
- Conditions
- Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations, Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations
- Being tested
- TAS-117
- Keywords
- TAS-117, AKT inhibitor, Allosteric inhibitor, Advanced solid tumor, Metastatic solid tumor, PTEN, Germline PTEN, Inactivating mutation, Adolescent patients, Adult patients
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAS-117Drug
TAS-117 will be dosed orally every day on a 21-day cycle
TAS-117Drug
TAS-117 will be dosed intermittently on a 21-day cycle
TAS-117Drug
TAS-117 will be dosed orally every day or intermittently on a 21-day cycle
TAS-117Drug
TAS-117 will be dosed orally every day or intermittently on a 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in) | Experimental | Advanced or metastatic solid tumors irrespective of gene alterations Receives: Drug: TAS-117 |
| TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in) | Experimental | Advanced or metastatic solid tumors irrespective of gene alterations Receives: Drug: TAS-117 |
| TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in) | Experimental | Advanced or metastatic solid tumors with germline PTEN inactivating mutations Receives: Drug: TAS-117 |
| TAS-117 Phase 2 (Part B) | Experimental | Advanced or metastatic solid tumors with germline PTEN inactivating mutations Receives: Drug: TAS-117 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events and dose-limiting toxicities (safety and tolerability) and MTD of TAS-117 in Part A
Number of patients with abnormal laboratory values, treatment emergent AEs, abnormal vital signs and ECG, and Dose-limiting toxicities (DLTs)
Measured: 21 days for DLT evaluation, approximately 7 months for the others
Recommended Phase 2 Dose (RP2D) of TAS-117 in Part A
Measured: 21 days for DLT evaluation, approximately 7 months for the others
Objective Response Rate (ORR) in Part B (including all patients with germline PTEN mutations in Part A)
ORR, defined as the proportion of patients experiencing a best overall response of CR or PR per RECIST 1.1.
Measured: Approximately 6 months
Secondary outcomes (10)
Incidence of treatment-emergent adverse events (safety) in Part B
Number of patients with abnormal laboratory values, treatment-emergent AEs, abnormal vital signs and ECG
Measured: Approximately 7 months
Disease Control Rate (DCR)
DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR).
Measured: Approximately 6 months
Duration of Response (DOR)
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.
Measured: Approximately 6 months
Progression Free Survival (PFS)
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.
Measured: Approximately 6 months
Overall Survival (OS)
OS, defined as the time from the date of first dose to the death date.
Measured: Approximately 12 months
Pharmacokinetics (PK) profile of TAS-117 in Part A
maximum plasma concentration (Cmax)
Measured: 21 days
Pharmacokinetics (PK) profile of TAS-117 in Part A
area under the plasma concentration-time curve (AUC)
Measured: 21 days
Pharmacokinetics (PK) profile of TAS-117 in Part A
time to reach maximum plasma concentration (Tmax)
Measured: 21 days
Pharmacokinetics (PK) profile of TAS-117 in Part A
terminal elimination half-life (T1/2)
Measured: 21 days
Pharmacodynamics (PD) profile of TAS-117 in Part A
Evaluate Total and Phosphorylated AKT and PRAS40
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start31 Mar 2021
- Primary completion28 Feb 2023
- Study completion6 Mar 2023
Why it stopped: The Sponsor had decided to terminate this clinical trial due to an insufficient rate of accrual of patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced or Metastatic Solid Tumors Irrespective of Gene AlterationsStudies of the same condition, open and under way.
- More trials run by Taiho Oncology, Inc.The 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04770246
- Sponsor's protocol ID
- TAS-117-201
- Other IDs
- 2020-004770-22
- Status last verified
- Aug 2024
- First submitted
- 16 Feb 2021
- Last updated
- 4 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rodon J, Funchain P, Laetsch TW, Arkenau HT, Hervieu A, Singer CF, Murciano-Goroff YR, Chawla SP, Anthony K, Yamamiya I, Liu M, Halim AB, Benhadji KA, Takahashi O, Delaloge S. A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations. Future Oncol. 2022 Sep;18(30):3377-3387. doi: 10.2217/fon-2022-0305. Epub 2022 Aug 30.
PubMed 36039910
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations
- ClinicalTrials.gov ID
- NCT04770246
- Acronym / sponsor ID
- TAS-117-201
- Conditions
- Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations, Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations
- Keywords
- TAS-117, AKT inhibitor, Allosteric inhibitor, Advanced solid tumor, Metastatic solid tumor, PTEN, Germline PTEN, Inactivating mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor had decided to terminate this clinical trial due to an insufficient rate of accrual of patients.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Taiho Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Mar 2021 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 6 Mar 2023 (actual)
- First posted
- 25 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in) | Experimental | Drug: TAS-117Advanced or metastatic solid tumors irrespective of gene alterations |
| TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in) | Experimental | Drug: TAS-117Advanced or metastatic solid tumors irrespective of gene alterations |
| TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in) | Experimental | Drug: TAS-117Advanced or metastatic solid tumors with germline PTEN inactivating mutations |
| TAS-117 Phase 2 (Part B) | Experimental | Drug: TAS-117Advanced or metastatic solid tumors with germline PTEN inactivating mutations |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Dose Escalation in Part A
- Dose and Regimen Confirmation in Part A and Phase 2 (Part B)
Key exclusion criteria (6 listed)
- History or current evidence of interstitial lung disease that requires steroid medication.
- Current evidence of diabetes mellitus that requires insulin therapy.
- Prior treatment with PI3K/AKT/mTOR pathway inhibitors.
- Patients with primary brain tumor.
- Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastasis.
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 |
|---|---|---|
| TAS-117TAS-117 will be dosed orally every day on a 21-day cycle | Drug | TAS-117 Dose Escalation Daily Dose Regimen (Part A: safety lead-in) |
| TAS-117TAS-117 will be dosed intermittently on a 21-day cycle | Drug | TAS-117 Dose Escalation Intermittent Dose Regimen (Part A: safety lead-in) |
| TAS-117TAS-117 will be dosed orally every day or intermittently on a 21-day cycle | Drug | TAS-117 Dose and Regimen Confirmation (Part A: safety lead-in) |
| TAS-117TAS-117 will be dosed orally every day or intermittently on a 21-day cycle | Drug | TAS-117 Phase 2 (Part B) |
Primary outcome
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)
Recommended Phase 2 Dose (RP2D) of TAS-117 in Part A
Time frame: 21 days for DLT evaluation, approximately 7 months for the others
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.
10 secondary outcomes
Incidence of treatment-emergent adverse events (safety) in Part B
Time frame: Approximately 7 months
Disease Control Rate (DCR)
Time frame: Approximately 6 months
Duration of Response (DOR)
Time frame: Approximately 6 months
Progression Free Survival (PFS)
Time frame: Approximately 6 months
Overall Survival (OS)
Time frame: Approximately 12 months
Pharmacokinetics (PK) profile of TAS-117 in Part A
Time frame: 21 days
Pharmacokinetics (PK) profile of TAS-117 in Part A
Time frame: 21 days
Pharmacokinetics (PK) profile of TAS-117 in Part A
Time frame: 21 days
Pharmacokinetics (PK) profile of TAS-117 in Part A
Time frame: 21 days
Pharmacodynamics (PD) profile of TAS-117 in Part A
Time frame: 21 days
Results and safety
The study was stopped early (reason given: The Sponsor had decided to terminate this clinical trial due to an insufficient rate of accrual of patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Derived from this study: PubMed 36039910Rodon J, Funchain P, Laetsch TW, Arkenau HT, Hervieu A, Singer CF, Murciano-Goroff YR, Chawla SP, Anthony K, Yamamiya I, Liu M, Halim AB, Benhadji KA, Takahashi O, Delaloge S. A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN-inactivating mutations. Future Oncol. 2022 Sep;18(30):3377-3387. doi: 10.2217/fon-2022-0305. Epub 2022 Aug 30.
- Individual participant dataSharing planned: No
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.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAS-117 in people with Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations and Advanced or Metastatic Solid Tumors With Germline PTEN Inactivating Mutations, run by Taiho Oncology, Inc. at 8 sites in 4 countries.
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 13 inclusion and 6 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: stopped early, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Austria, France, United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The Sponsor had decided to terminate this clinical trial due to an insufficient rate of accrual of patients.). Results are not available in the source record.
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?
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). The study lists 3 primary outcomes in all. 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 NCT04770246, 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 4 Sep 2024.