Ascending Doses of AZD6738 in Combination With Chemotherapy and/or Novel Anti Cancer Agents
Conditions
Advanced Solid Malignancies, ATM Deficient NSCLC Adenocarcinoma, Gastric Cancer, Gastro-oesophageal Junction
Conditions: official terms
Adenocarcinoma - Neoplasms
Conditions: Keywords
ATM deficient
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Administration of AZD6738 in combination with carboplatin Type: Drug
Name: Administration of AZD6738 Type: Drug
Name: Administration of AZD6738 in combination with olaparib Type: Drug
Overall Status
Recruiting
Summary
This is a modular, phase I/ phase 1 b, open-label, multicentre study of AZD6738 administered orally in combination with cytotoxic chemotherapy regimens and/or novel anti-cancer agents, to patients with advanced malignancies. The study design allows an investigation of optimal combination dose of AZD6738 with other anti-cancer treatments, with intensive safety monitoring to ensure the safety of the patients. The initial combination to be investigated is AZD6738 with carboplatin. The second combination to be investigated is AZD6738 with Olaparib
Detailed Description
This is a modular, phase I, 2 part, open-label, multicentre study of AZD6738, administered orally, in combination with cytotoxic chemotherapy regimens and/or novel anti-cancer agents, to patients with advanced/metastatic solid malignancies. The study design allows an escalation of the dose of AZD6738 in combination with the standard dose and schedule of either cytotoxic chemotherapies and/or novel anti-cancer agents, with intensive safety monitoring to ensure the safety of the patients. There are two parts to each combination module of this study; part A, dose escalation and an optional part B, cohort expansions in particular patient groups. The initial combination module will be with Carboplatin (module 1). The second combination will be with Olaparib (module 2). The option to start further combination modules will be the decision of the Safety Review Committee (SRC), based on emerging preclinical data and, safety and tolerability information from the initial combination. Combinations of AZD6738 with novel anti-cancer agents may also be explored. Once a minimally biologically active dose of AZD6738, for that combination module, has been identified from part A of that module, the SRC may decide to commence part B if deemed to be necessary. This may include cohort expansions of specific patient groups to explore preliminary anti-tumour activity or the effect of food or particular drug combinations on drug pharmacokinetics.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Principal Inclusion criteria:

- Aged at least 18

- The presence of a solid malignant tumour that is not considered appropriate for further standard treatment

- Module 1 and 2 Part B Study expansion: Recurrence on or within 6 months of last platinum based therapy

- Module 1 and 2 Part B Study expansion: patients must have a tumour at least 1 cm in size that can be measured using a CT or MRI scan

- Module 1 Part B Study expansion: two groups of patients: second line lung adenocarcinoma with ATM deficient tumours, or platinum-resistant high grade serous ovarian cancer.

- Module 2 Part B Study expansion: two groups of advanced gastric adenocarcinoma (including GEJ) patients with ATM deficient tumours: no previous treatment with PARP inhibitor, or any previous treatment with PARP inhibitor.

Principal exclusion criteria

- A diagnosis of ataxia telangiectasia

- Prior exposure to an ATR inhibitor

- Bad reaction to AZD6738

- Module 1: Contra-indicated for treatment with carboplatin

- Module 2: Contra-indicated for treatment with olaparib
Locations
Research Site
Los Angeles, California, United States
Status: Recruiting
Research Site
Villejuif, France
Status: Recruiting
Research Site
Manchester, United Kingdom
Status: Recruiting
Research Site
Sutton, United Kingdom
Status: Recruiting
Start Date
October 2014
Completion Date
September 2017
Sponsors
AstraZeneca
Source
AstraZeneca
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page