Advanced Gastric Adenocarcinoma
Conditions
Brief summary
This is a Phase Ib/IIa, open-label, non-randomized, dose-escalation, multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of oral GSK2636771 in combination with intravenous (IV) paclitaxel in two independent subject populations: subjects with PTEN-deficient, advanced gastric adenocarcinoma.
Detailed description
This is a Phase Ib/IIa, open-label, non-randomized, dose-escalation, multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of oral GSK2636771 in combination with intravenous (IV) paclitaxel in two independent subject populations: subjects with PTEN-deficient, advanced gastric adenocarcinoma. This study will be conducted in two phases: the Dose Escalation Phase and the Dose Expansion Phase. The Dose Escalation Phase (Phase Ib) is designed to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) of GSK2636771 administered in combination with paclitaxel. The Dose Expansion Phase (Phase IIa) will further evaluate the safety and clinical activity of the RP2D as determined in the Dose Escalation Phase.
Interventions
DRUGGSK2636771
Increasing dose levels of GSK2636771 (300 mg or 400 mg once daily)
DRUGPaclitaxel
fixed dose of paclitaxel (80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle)
Sponsors
Yonsei University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. histologically or cytologically confirmed diagnosis of advanced gastric adenocarcinoma 2. Has a PTEN-deficient tumor as documented from archival or fresh (from biopsy) tumor tissue or has shown genomic alterations in PI3K pathway genes (PIK3CB, PI3KR1, PTEN, etc.) as assessed in a local laboratory. 3. Has had no prior taxane exposure (preferred) or at least 6 months since last taxane exposure. 4. Eastern Cooperative Oncology Group performance status of 0 or 1 5. measurable or evaluable disease as determined by RECIST 1.1. 6. Is able to swallow and retain orally administered medication 7. adequate baseline organ function
Exclusion criteria
1. prior treatment with any AKT, mammalian target of rapamycin (mTOR) inhibitors or PI3K pathway inhibitors 2. Has any unresolved Grade 2 (per CTCAE v4.0) toxicity from previous anti-cancer therapy at the time of enrollment such as neuropathy, except alopecia or Grade 2 anemia (if hemoglobin is ≥9.0 g/dL) 3. Has CNS metastases 4. Has a QTc interval \>450 msec or QTc \>480 msec for subjects with bundle branch block (BBB) 5. Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2636771 or hypersensitivity to drug formulated in polyoxyl 35 castor oil, NF such as paclitaxel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase II dose | 4 weeks | Recommended Phase II dose for phase 1 |
| Progression-free survival | 6 weeks | Progression-free survival for phase 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity | 28 days | Dose limiting toxicity for phase 1 |
Countries
South Korea
Outcome results
None listed