Advanced or Metastatic Solid Tumors
Conditions
Keywords
Solid Tumors, AKT inhibitor, RSK inhibitor, S6K inhibitor, kinase inhibitor, phase I, Prostate cancer, PTEN loss, PTEN mutation
Brief summary
The purpose of this study is to see if TAS0612 is safe in participants with advanced or metastatic solid tumor cancer.
Interventions
DRUGTAS0612
oral tablets
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) | Baseline through Cycle 1 (28-day cycle) | Number of participants with DLTs during cycle 1 |
| rPFS rate | Baseline through measured progressive disease (estimated up to 12 months) | Percentage of participants with partial response (PR) or complete response (CR) at 6 months Prostate Cancer Working Group 3 (PCWG3)/ modified defined by the Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) parameters including but not limited to: Cmax | Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1 | time of TAS0612 it takes to reach Cmax. |
| Safety and Tolerability | From screening to 30 days after last dose | All adverse events (AEs) per CTCAE v5.0. |
| Pharmacodynamic: biochemical effects of TAS0612: Total proteins | Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) | Total proteins will be measured in blood samples collected at different time points. |
| Pharmacodynamic: biochemical effects of TAS0612: phospho-proteins | Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) | Phospho-proteins will be measured in blood samples collected at different time points. The levels/changes (dose- and concentration-dependent) of phospho-proteins will be assessed and reported for biochemical effects of TAS0612. |
| Pharmacodynamic: molecular effects in tumor tissue of TAS0612 | Baseline through Day 1 Cycle 2 (28-day cycle) through study completion, an average of 1 year | Selected phospho-proteins will be analyzed in tumor tissue at baseline and on-treatment in dose escalation. The levels/changes of the phospho-proteins will be assessed and reported for target modulation. |
| Duration of Response (DOR) per PCWG3/mRECIST1.1 | Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months. | DOR: Date of PR or CR to date of objective progression or death due to any cause. |
| Disease Control Rate (DCR) per PCWG3/mRECIST1.1 | Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months. | DCR: Percentage of participants who exhibit stable disease (SD), PR or CR. |
| Radiographic Progression Free Survival (rPFS) per PCWG3/mRECIST1.1 | Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 6 months. | Proportion of patients experiencing a radiographic progression by PCWG3/mRECIST1.1 criteria |
| Overall Response Rate (ORR) per PCWG3/mRECIST1.1 | Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months. | Proportion of patients experiencing a best overall response of Complete Response (CR) or Partial response (PR) |
| Prostatic Specific Antigen (PSA) Response | Baseline to PSA progression, up to 12 months | Proportion of patients with ≥50% reduction in PSA from baseline to lowest post-baseline result. |
| Pharmacokinetics (PK) parameters including but not limited to: Tmax | Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1 | time of TAS0612 it takes to reach Cmax, |
| Pharmacokinetics (PK) parameters including but not limited to: AUC. | Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1 | Area under the plasma concentration curve of TAS0612. |
| Pharmacokinetics (PK) parameters including but not limited to: T1/2. | Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1 | time it takes for plasma concentration to fall by half its original value (t1/2) of TAS0612 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exposure of TAS0612 and selected efficacy and safety measures. | Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months. | To explore the correlation between PK and antitumor activity or toxicity |
| Time-matched plasma exposures of TAS0612 and changes from baseline in QTcF using central ECG measurements | Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months | To explore the correlation between the incidence of exposures of TAS0612 in plasma and QT prolongation |
| Exploratory correlation of tissue and/or blood markers with tumor efficacy endpoints and/or tumor resistance to TAS0612 | Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months. | To investigate potential predictive biomarkers for TAS0612. |
| Pharmacokinetics (PK): Metabolites in plasma | Cycle 1 Day 1 (each cycle is 28 days). | Structure elucidation of TAS0612 metabolites in human plasma. |
Countries
France, United States
Outcome results
None listed