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

Brief summary public domain (ClinicalTrials.gov)

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

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) of cediranib (cediranib maleate) plus olaparib in combination in patients with advanced or metastatic solid tumors of the following tumor types: non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC). SECONDARY OBJECTIVES: I. To assess the safety and tolerability of oral administration of cediranib in combination with olaparib in patients with select advanced solid tumors. II. To estimate progression free survival (PFS) in each tumor cohort. EXPLORATORY OBJECTIVES: I. To estimate the prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in tumors using the BROCA panel and to correlate tumor regression with mutations status. (Integrated) II. To evaluate changes in tumor 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 levels of angiogenesis/inflammatory markers including VEGF at baseline and on treatment. IV. To evaluate levels of circulating tumor deoxyribonucleic acid (ctDNA) at baseline and on treatment. OUTLINE: Patients receive cediranib maleate orally (PO) once daily (QD) on day 1. Patients undergoing FMISO scan also receive olaparib PO twice daily (BID) beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks. Patients who discontinue the study treatment for reasons other than disease progression or withdrawal of consent will continue to be followed every 4 weeks until disease progression, start of new therapy, or death, whichever occurs first.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Objective Response Rate [Up to 4 weeks after completion of study treatment (Up to 43 months)]. Number, proportion of participants (95% Confidence Interval). NSCLC Cohort (n=26): 0.08 (0.01 to 0.15); TNBC Cohort (n=37): 0.16 (0.09 to 0.24); SCLC Cohort (n=27): 0.26 (0.16 to 0.36); PDAC Cohort (n=19): 0 (NA to NA) [There were no responders in this cohort.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Incidence of Adverse Events [Up to 4 weeks after completion of study treatment (Up to 44 months)]. Number, Adverse Events. Grade 3: NSCLC Cohort (n=29): 60; TNBC Cohort (n=38): 71; PDAC Cohort (n=19): 37; SCLC Cohort (n=27): 61. Grade 4: NSCLC Cohort (n=29): 2; TNBC Cohort (n=38): 1; PDAC Cohort (n=19): 2; SCLC Cohort (n=27): 7.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival [Up to 4 weeks after completion of study treatment (Up to 44 months)]. Median, months (Full Range). NSCLC Cohort (n=26): 3.8 (0.1 to 13.3); TNBC Cohort (n=37): 3.4 (1.4 to 42.7); PDAC Cohort (n=19): 1.8 (1.8 to 7.5); SCLC Cohort (n=27): 4.0 (0.8 to 14.5).