A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumours

Official Title

A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumours

Summary:

This phase II trial studies cediranib maleate in combination with olaparib in treating patients with solid tumours that have spread to other parts of the body or cannot be removed by surgery, including breast cancer, non-small cell lung cancer, small cell lung cancer, and pancreatic cancer. Cediranib maleate and olaparib may stop the growth of tumour cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may also block the flow of oxygen to the tumour, and may help make the tumour more sensitive to olaparib.

Trial Description

Primary Outcome:

• Objective response rate, measured by Response Evaluation Criteria in Solid Tumours version 1.1

Secondary Outcome:

• Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
• Progression-free survival

PRIMARY OBJECTIVES:
I. To determine the objective response rate (ORR) of cediranib (cediranib maleate) plus olaparib in combination in patients with advanced or metastatic solid tumours of the following tumour types: non-small cell lung cancer (NSCLC), germline breast cancer, early onset 1/2 (BRCA1/2) wild type (wt), basaloid triple negative breast cancer (b-TNBC), pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC). The responses will be assessed by the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of oral administration of cediranib in combination with olaparib in patients with select advanced solid tumours. II. To determine progression free survival (PFS) in each tumour cohort. TERTIARY OBJECTIVES:
I. To estimate the prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in tumours using the BROCA panel and to correlate tumour regression with mutations status. (Integrated) II. To evaluate changes in tumour hypoxia on cediranib treatment compared to baseline by [F-18] fluoromisonidazole (FMISO) positron emission tomography/computed tomography (PET/CT) in patients with NSCLC. III. To evaluate BRCA1 expression in patients with NSCLC or basaloid TNBC at baseline and changes on 4 days of cediranib treatment in the NSCLC and TNBC cohorts. IV. To evaluate hypoxia markers at baseline and changes on treatment with cediranib in tumour tissue in the NSCLC and TNBC cohorts. V. To evaluate levels of angiogenesis/inflammatory markers including VEGF at baseline and on treatment. VI. To evaluate levels of hypoxia-related microribonucleic acids (miRNAs) at baseline and on treatment. OUTLINE:

Patients receive cediranib maleate orally (PO) once daily (QD) for 3-4 days and then undergo biopsy. After biopsy, patients continue to receive cediranib maleate PO QD and begin olaparib PO twice daily (BID) beginning on the day after the post-dose biopsy (days 4-7) or by day 8 of course 1 (biopsy cohorts-NSCLC and TNBC) or day 4 of course 1 (non-biopsy cohorts-PDAC and SCLC). Courses repeat every 28 days (35 days for course 1) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

View this trial on ClinicalTrials.gov