Basket Combination Study of Inhibitors of DNA Damage Response, Angiogenesis and Programmed Death Ligand 1 in Patients With Advanced Solid Tumours

Official Title

Basket Combination Study of Inhibitors of DNA Damage Response, Angiogenesis and Programmed Death Ligand 1 in Patients With Advanced Solid Tumours

Summary:

This is a phase 2, single-centre, randomized, multi-cohort trial of subjects with advanced Mismatch Repair Proficient Colorectal Cancer (MMRp-CRC), Pancreatic Adenocarcinoma (PA), and Leiomyosarcoma (LMS). Subjects will be stratified based on their primary malignancy and enrolled into one of the following cohorts: - Cohort A: olaparib and durvalumab. - Cohort B: cediranib and durvalumab. Subjects will receive durvalumab through an intravenous line every 4 weeks. If subjects are assigned to the olaparib group, then they will take this pill twice a day continuously. If subjects are assigned to the cediranib group, then they will take this pill once a day for 5 consecutive days, and then have 2 consecutive days off, every week. Subjects will be enrolled in this trial to evaluate the changes in genomic and immune biomarkers in tumour, peripheral blood and stool samples, in addition to changes in radiomic profiles. About 90 people (45 subjects in each cohort) will be enrolled into this study at the Princess Margaret Cancer Centre.

Trial Description

Primary Outcome:

• Changes in genomic and immune biomarkers that will be measured in the baseline biopsy and the first on-treatment biopsy by applying a log-transformation and the t-test.

Secondary Outcome:

• Overall response rate (ORR)
• Clinical benefit rate (CBR)
• Progression-free survival (PFS)
• Overall survival (OS)
• Antitumour activity based on iRECIST
• Incidence of treatment-emergent adverse events (AEs)

The goal of this study is to evaluate the changes in genomic and immune biomarkers in tumour, peripheral blood and stool samples, in addition to changes in radiomic profiles, of subjects with advanced Mismatch Repair Proficient Coloretal Cancer (MMRp-CRC), Pancreatic Adenocarcinoma (PA), or Leiomyosarcoma (LMS) during combination treatment of durvalumab (inhibitor of PD-L1) with either olaparib (inhibitor of Poly (ADP-ribose) polymerase [PARP]) or cediranib (inhibitor of Vascular Endothelial Growth Factor Receptor [VEGFR] tyrosine kinases).

View this trial on ClinicalTrials.gov