PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma

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 Having Alterations in PI3K Pathway Genes

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.

Study Overview

• Status: Completed
• Conditions: Advanced Gastric Adenocarcinoma
• Intervention / Treatment: Drug: GSK2636771; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System, Yonsei Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: GSK2636771; Increasing dose levels of GSK2636771 (300 mg or 400 mg once daily); Drug: Paclitaxel; fixed dose of paclitaxel (80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recommended Phase II dose for phase 1	4 weeks
Progression-free survival for phase 2	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Dose limiting toxicity for phase 1	28 days

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Sun Young Rha, Yonsei Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: November 24, 2015
• First Submitted That Met QC Criteria: November 24, 2015
• First Posted (Estimate): November 26, 2015

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; GSK2636771
• Other Study ID Numbers: 4-2015-0204