Clinical Trials /

PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma

NCT02615730

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.

Related Conditions:
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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 Having Alterations in PI3K Pathway Genes

Clinical Trial IDs

  • ORG STUDY ID: 4-2015-0204
  • NCT ID: NCT02615730

Conditions

  • Advanced Gastric Adenocarcinoma

Interventions

DrugSynonymsArms
GSK2636771Paclitaxel & GSK2636771
PaclitaxelPaclitaxel & GSK2636771

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Paclitaxel & GSK2636771ExperimentalIncreasing 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)
  • GSK2636771
  • Paclitaxel

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase II dose for phase 1
Time Frame:4 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Dose limiting toxicity for phase 1
Time Frame:28 days
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yonsei University

Last Updated

January 10, 2018