PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma

Advanced Gastric Adenocarcinoma Clinical Trial

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 Having Alterations in PI3K Pathway Genes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02615730
• Other study ID #: 4-2015-0204
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2016
• Est. completion date: March 31, 2021

Study information

• Verified date: April 2021
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Gastric Adenocarcinoma

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Severance Hospital, Yonsei University Health System, Yonsei Cancer Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase II dose for phase 1		4 weeks
Primary	Progression-free survival for phase 2		6 weeks
Secondary	Dose limiting toxicity for phase 1		28 days