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Ascending Doses of Ceralasertib in Combination With Chemotherapy and / or Novel Anti Cancer Agents

Trial Status: Active

This is a modular, phase I / phase 1 b, open-label, multicentre study of ceralasertib 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 ceralasertib with other anti-cancer treatments, with intensive safety monitoring to ensure the safety of the patients. The initial combination to be investigated is ceralasertib with carboplatin. The second combination to be investigated is ceralasertib with Olaparib. The third combination to be investigated is ceralasertib with durvalumab

Inclusion 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 expansions, and Module 3: 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: second line lung adenocarcinoma with ATM deficient tumours. - Module 2 Part B All - No previous treatment with PARP inhibitor. - Module 2 Part B1 Study expansion: advanced gastric adenocarcinoma (including GEJ) patients with ATM deficient tumours - Module 2 Part B2 Study expansion: advanced gastric adenocarcinoma (including GEJ) patients with ATM proficient tumours - Module2 Part B3 Study expansion: Second or thrid line HER2 negative breast cancer - Module 2 Part B4 Study expansion: Second or third line triple negative breast cancer (TNBC) - Module 2 Part B5 Study expansion: BRCA mutant or RAD51C/D mutant or HRD positive status ovarian cancer patient who are Platinum sensitive and have previously progressed on a licensed PARPi - Module 3: advanced recurrent or metastatic non-small cell lung cancer, or head and neck squamous cell carcinoma Principal exclusion criteria - A diagnosis of ataxia telangiectasia - Prior exposure to an ATR inhibitor - Bad reaction to ceralasertib - Module 1: Contra-indicated for treatment with carboplatin - Module 2: Contra-indicated for treatment with olaparib - Module 3: Contra-indicated for treatment with durvalumab

California

Duarte
City of Hope Comprehensive Cancer Center
Status: APPROVED
Los Angeles
Los Angeles County-USC Medical Center
Status: ACTIVE
Contact: Xiomara Menendez
Phone: 323-865-0212
USC / Norris Comprehensive Cancer Center
Status: ACTIVE
Newport Beach
Hoag Memorial Hospital
Status: ACTIVE
Contact: Cristina de Leon
Phone: 949-764-5543

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: COMPLETED

This is a modular, phase I, two part, open-label, multicentre study of ceralasertib,

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 ceralasertib 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 third

combination will be with durvalumab (module 3). 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 ceralasertib with novel anti-cancer agents may also be explored. Once a

minimally biologically active dose of ceralasertib, 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.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
AstraZeneca Pharmaceuticals LP

  • Primary ID D5330C00004
  • Secondary IDs NCI-2015-00687
  • Clinicaltrials.gov ID NCT02264678