Clinical trial NCT04586270: A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer
Official title: A Phase 1 Study of TAS0612 in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Keywords: Solid Tumors
AKT inhibitor
RSK inhibitor
S6K inhibitor
kinase inhibitor
phase I
Prostate cancer
PTEN loss
PTEN mutation
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-14
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if TAS0612 is safe in participants with advanced or metastatic solid tumor cancer.


Eligibility criteria: Inclusion Criteria:

Dose Escalation:

Have histologically confirmed, locally advanced, and unresectable cancer, or metastatic cancer and have progressed on or were intolerant to standard treatments or refused standard of care (SOC).

Dose Expansion:

Have documented histologically or cytologically confirmed adenocarcinoma of the prostate with documented PTEN loss or loss of function mutation, who have metastatic castration-resistant disease and have:

* Disease progression per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3)/modified RECIST 1.1 after the most recent regimen.
* Received androgen receptor directed therapy previously with or without chemotherapy consisting of no more than 2 prior taxane-based regimens.
* Been receiving androgen deprivation therapy with serum testosterone \<50 ng/dL (\<2.0 nM). Note: previously documented PTEN loss or loss of function mutation from archived tissue sample testing or cfDNA sample testing is acceptable if done in a CLIA certified lab or a locally certified lab.

Have an ECOG score of 0 or 1 Dose Escalation (Part 1): Have no measurable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Dose Expansion (Part 2): Have measurable or no measurable disease per PCWG3/modified RECIST 1.1

• No more than 30 patients with no measurable disease will be enrolled in Dose Expansion (Part 2).

Exclusion Criteria:

* Participating in medical research not compatible with this study
* Have not discontinued or recovered from previous treatments for cancer
* Have a significant cardiac condition
* Have untreated brain metastases
* Have a primary brain tumor
* Have a serious concomitant disorder
* Unable to swallow or digest pills
* Poorly controlled diabetes
* Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs)
timeFrame: Baseline through Cycle 1 (28-day cycle)
measure: rPFS rate
timeFrame: Baseline through measured progressive disease (estimated up to 12 months)
Secondary outcomes:
measure: Disease Control Rate (DCR) per PCWG3/mRECIST1.1
timeFrame: Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
measure: Duration of Response (DOR) per PCWG3/mRECIST1.1
timeFrame: Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
measure: Radiographic Progression Free Survival (rPFS) per PCWG3/mRECIST1.1
timeFrame: Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 6 months.
measure: Overall Response Rate (ORR) per PCWG3/mRECIST1.1
timeFrame: Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
measure: Prostatic Specific Antigen (PSA) Response
timeFrame: Baseline to PSA progression, up to 12 months
measure: Pharmacokinetics (PK) parameters including but not limited to: Cmax
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
measure: Pharmacokinetics (PK) parameters including but not limited to: Tmax
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
measure: Pharmacokinetics (PK) parameters including but not limited to: AUC.
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
measure: Pharmacokinetics (PK) parameters including but not limited to: T1/2.
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
measure: Safety and Tolerability
timeFrame: From screening to 30 days after last dose
measure: Pharmacodynamic: biochemical effects of TAS0612: Total proteins
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle)
measure: Pharmacodynamic: biochemical effects of TAS0612: phospho-proteins
timeFrame: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle)
measure: Pharmacodynamic: molecular effects in tumor tissue of TAS0612
timeFrame: Baseline through Day 1 Cycle 2 (28-day cycle) through study completion, an average of 1 year
Other outcomes:
measure: Pharmacokinetics (PK): Metabolites in plasma
timeFrame: Cycle 1 Day 1 (each cycle is 28 days).
measure: Time-matched plasma exposures of TAS0612 and changes from baseline in QTcF using central ECG measurements
timeFrame: Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months
measure: Exploratory correlation of tissue and/or blood markers with tumor efficacy endpoints and/or tumor resistance to TAS0612
timeFrame: Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
measure: Exposure of TAS0612 and selected efficacy and safety measures.
timeFrame: Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
Locations:
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Marseille
country: France
facility: Institut Paoli Calmette
state: Bouches Du Rhone
city: Villejuif
country: France
facility: Centre de Lutte Contre le Cancer Gustave Roussy
state: Val De Marne
Study officials:
References: