Clinical trial NCT02615730: PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma
Official title: A Phase Ib/IIa, Open-Label, Dose Finding Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of PI3Kβ Selective Inhibitor (GSK2636771) Administered in Combination With Paclitaxel in Advanced Gastric Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Gastric Adenocarcinoma
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2015-11-26
Enrollment: 42
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recommended Phase II dose
timeFrame: 4 weeks
measure: Progression-free survival
timeFrame: 6 weeks
Secondary outcomes:
measure: Dose limiting toxicity
timeFrame: 28 days
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System, Yonsei Cancer Center
Study officials:
affiliation: Yonsei Cancer Center
name: Sun Young Rha
role: PRINCIPAL_INVESTIGATOR
References: