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

NCT02449655 | Terminated Phase 2

• 1 other identifier: 2014-04-122
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  expected average of 24 weeks

Secondary Outcomes (6)

• Duration of response

  expected average of 24 weeks

• Disease control rate

  8 weeks

• Overall survival (OS)

  expected average of 24 weeks

• progression-free survival (PFS)

  expected average of 24 weeks

• Biomarker analysis

  3 years

Study Arms (2)

AZD5363 plus paclitaxel

EXPERIMENTAL

AZD5363 4800mg 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.

Drug: AZD5363; Drug: paclitaxel

AZD2014 plus paclitaxel

ACTIVE COMPARATOR

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

Drug: AZD2014; Drug: paclitaxel

Interventions

AZD5363 DRUG

AZD5363 4800mg bid 4 days on/ 3 days off of a 7 day cycle for each week

AZD5363 plus paclitaxel

paclitaxel DRUG

paclitaxel 80mg/m2 given days 1, 8 and 15 of a 28 day cycle

AZD5363 plus paclitaxel

AZD2014 DRUG

AZD2014 50mg BD 3 days on 4 days off of a 7 day cycle

AZD2014 plus paclitaxel

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of fully informed consent prior to any study specific procedures.
• Patients must be ≥20 years of age.
• Advanced gastric adenocarcinoma that has progressed during or after first-line therapy.
• The 1st line regimen must have contained doublet 5-fluoropyrimidine and platinum based regimen.
• Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doublet 5-fluoropyrimidine and platinum-based regimen could be considered as first line therapy.
• Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first line therapy.
• Provision of tumor sample (from either a resection or biopsy)
• Patients with biomarker negative
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• Eastern Cooperative Oncology Group performance status 0-1.
• Patients must have a life expectancy ≥ 3 months from proposed first dose date.
• Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥9.0 g/dL (transfusion allowed)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• White blood cells (WBC) \> 3 x 109/L

You may not qualify if:

• More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting.
• Any previous treatment with PIK3CA, AKT or mTOR inhibitor or agents with mixed PI3K / mTOR activity.
• Any previous treatment with paclitaxel
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≤5 years.
• HER2 positive patients
• Patients unable to swallow orally administered medication.
• Any investigational drug or product administered within 30 days or 5 half-lives, whichever is longer, of the first dose of AZD5363.
• Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
• Previous major surgery within 4weeks prior to enrollment.
• For AZD2014: Exposure to potent or moderate inhibitors or inducers of CYP3A4/5 if taken within the stated washout periods before the first dose of study treatment
• With the exception of alopecia, any ongoing toxicities (\>Common Toxicity Criteria for Adverse Effects grade 1) caused by previous cancer therapy.
• Intestinal obstruction or Common Toxicity Criteria for Adverse Effects grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
• Resting ECG with measurable QTcB \> 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) Left ventricular ejection fraction \<55% measured by echocardiography, Atrial fibrillation with a ventricular rate \>100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment
• Active or untreated brain metastases or spinal cord compression Patients with treated brain metastases or spinal cord compression are eligible if they have minimal neurologic symptoms, evidence of stable disease (for at least 1 month) or response on follow-up scan, and require no corticosteroid therapy for ≥ 1 week.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical center

Seoul, 135-710, South Korea

Location

MeSH Terms

Interventions

capivasertib; Paclitaxel; vistusertib

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jee yun Lee, MD,Ph.D.

  Samsung Medical Center,Seoul,Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 20, 2015
• Study Start: February 12, 2015
• Primary Completion: July 16, 2018
• Study Completion: July 16, 2018
• Last Updated: May 20, 2019

Record last verified: 2019-05

Locations

KR (1)