NCT02449655

Trial of AZD5363 Plus Paclitaxel /AZD2014 Plus Paclitaxel in Biomarker Negative (PIK3CA/MEK/RAS/TP53/MET) Gastric Adenocarcinoma Patients as Second-line Chemotherapy

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: Samsung Medical Center · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

Phase II trial of AZD5363 plus paclitaxel / AZD2014 plus paclitaxel in biomarker negative (PIK3CA/MEK/RAS/TP53/MET) advanced gastric adenocarcinoma patients as second-line chemotherapy. Each arm is composed of 25 patients. AZD5363 400mg bid 4 days on/ 3 days off of a 7 day cycle for each week that paclitaxel is given + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle. AZD5363 and paclitaxel will be received for 3 consecutive weeks, followed by one week off-therapy in 4-week cycles.If paclitaxel therapy is stopped then AZD5363 can be given on a 4on/3off continuous schedule. AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle + paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle. Tumour evaluation using Response Evaluation Criteria in Solid Tumors 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date). Study treatment will be continued until objective disease progression. The purpose of this study is to investigate the safety and efficacy of AZD5363 plus paclitaxel in biomarker negative (PIK3CA/MEK/RAS/TP53/MET) advanced gastric adenocarcinoma patients as second-line chemotherapy.

Detailed description

AZD2014 is a selective dual mTOR kinase inhibitor targeting both mTORC1 (rapamycin sensitive) and mTORC2 (rapamycin insensitive) complexes of mammalian Target of Rapamycin (mTOR). AZD2014 is a selective dual mTOR kinase inhibitor targeting both mTORC1 (rapamycin sensitive) and mTORC2 (rapamycin insensitive) complexes of mammalian Target Of Rapamycin (mTOR) AZD2014 is specific for mTOR and does not inhibit other members of the PI3K superfamily. The PI3K-AKT-mTOR pathway functions as a sensor of mitogen, energy and nutrient levels and is a central controller of cell growth. The mTOR is a protein kinase (PK) and a vital component of the PI3K/Akt/mTOR signaling pathway. This pathway is deregulated in 50% of all human cancers and, as such, is an important target for inhibitors that would alleviate the unregulated proliferation of cancer cells . AZD2014 is selective inhibitor of mTOR kinases and inhibits signalling of both mTOR complexes, mTORC1 and mTORC2. In this study, the researchers further investigated the effect of PI3K/mTOR inhibitor as a paclitaxel sensitizer and/or nonspecific targeted therapy in combination with standard chemotherapy, paclitaxel in patients with pretreated advanced or metastatic gastric cancer having all negative biomarkers (PIK3CA/MEK/RAS/TP53/MET). AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50\<10nmol/l for all three AKT isoforms. AZD5363 is a highly potent adenosine triphosphate (ATP)-competitive AKT inhibitor with IC50\<10nmol/l for all three AKT isoforms. AKT pathway is activated in various human cancers.Although AKT inhibitor has known showing anti-tumor activity in cell lines mutated at the E542, E545, or H1047 positions in preclinical study, clinical studies with AKT inhibitor are conducted for non-selected cancer patients.

Conditions

• Advanced Gastric Adenocarcinoma

Interventions

Type	Name	Description
DRUG	AZD5363	AZD5363 4800mg bid 4 days on/ 3 days off of a 7 day cycle for each week
DRUG	paclitaxel	paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle
DRUG	AZD2014	AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle
DRUG	paclitaxel	paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle

Timeline

• Start date: 2015-02-12
• Primary completion: 2018-07-16
• Completion: 2018-07-16
• First posted: 2015-05-20
• Last updated: 2019-05-20

Locations

1 site across 1 country: South Korea