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.
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
Drug | Synonyms | Arms |
---|
GSK2636771 | | Paclitaxel & GSK2636771 |
Paclitaxel | | Paclitaxel & 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
Name | Type | Description | Interventions |
---|
Paclitaxel & GSK2636771 | Experimental | 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) | |
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: | Active, not recruiting |
Lead Sponsor: | Yonsei University |
Last Updated
October 19, 2020