PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma

NCT ID: NCT02615730

Last Updated: 2025-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2021-03-31

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.

Conditions

Advanced Gastric Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Paclitaxel & GSK2636771

Increasing dose levels of GSK2636771 (300 mg or 400 mg once daily) in combination with a fixed dose of paclitaxel (80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle)

Group Type: EXPERIMENTAL

GSK2636771

Intervention Type: DRUG

Increasing dose levels of GSK2636771 (300 mg or 400 mg once daily)

Paclitaxel

Intervention Type: DRUG

fixed dose of paclitaxel (80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle)

Interventions

GSK2636771

Increasing dose levels of GSK2636771 (300 mg or 400 mg once daily)

Intervention Type: DRUG

Paclitaxel

fixed dose of paclitaxel (80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Sun Young Rha

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sun Young Rha

Role: PRINCIPAL_INVESTIGATOR

Yonsei Cancer Center

Locations

Severance Hospital, Yonsei University Health System, Yonsei Cancer Center

Seoul, , South Korea

Countries

South Korea

Other Identifiers

4-2015-0204

Identifier Type: -

Identifier Source: org_study_id