Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Death

Leiomyosarcoma

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Sarcoma

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Angiogenesis Inhibitors

Durvalumab

Olaparib

Immunoglobulins

Immunoglobulin G

Complement System Proteins

Endothelial Growth Factors

Mitogens

Tyrosine Kinase Inhibitors

Immunoglobulins, Intravenous

Enzyme Inhibitors

Cediranib

Antineoplastic Agents, Immunological

Poly(ADP-ribose) Polymerase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Olaparib (given orally at a dose of 300 mg twice a day) in combination with Durvalumab (given intravenously at a dose of 1500 mg every 4 weeks)

Cediranib (given orally at a dose of 20 mg daily, 5 days on 2 days off) in combination with Durvalumab (given intravenously at a dose of 1500 mg every 4 weeks)

Durvalumab is a human immunoglobulin G (IgG)1 kappa monoclonal antibody directed against human PD-L1. Durvalumab selectively binds human PD-L1 with high affinity and blocks its ability to bind to PD-1 and cluster of differentiation (CD)80. The fragment crystallizable (Fc) domain of durvalumab contains a triple mutation in the constant domain of the IgG1 heavy chain that reduces binding to the complement component C1q and the Fc gamma receptors responsible for mediating antibody dependent cell mediated cytotoxicity.

Olaparib (AZD2281) is a potent oral poly Poly (ADP-ribose) Polymerase (PARP) enzyme inhibitor (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anti-cancer agents. Olaparib specifically traps PARP1 and PARP2 enzymes at sites of damaged DNA; the trapped PARP1- or PARP2-DNA complex is cytotoxic and produces clinical response. Although olaparib also binds to PARP3, recent investigations have suggested PARP-3 inhibition does not contribute towards anti-cancer activity.

Cediranib (AZD2171) is a potent oral small molecule Vascular Endothelial Growth Factor (VEGF) receptor tyrosine kinase inhibitor, specifically inhibiting all three VEGF receptors (VEGFR-1, -2 and -3). It has additional inhibitory activity against stem cell factor receptor tyrosine kinase, and less potency against platelet-derived growth factor receptor tyrosine kinases. Cediranib exerts its anti-angiogenic property by competitively inhibiting the ATP binding site on the VEGF receptors.

Lillian Siu, MD

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 tumor, 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.

The goal of this study is to evaluate the changes in genomic and immune biomarkers in tumor, 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).

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

If a departure from the normal distribution will be noticed for the distributions of the CD8 and CD4 then a log-transformation will be applied. The CD8 and CD4 will be compared between responders and non-responders by applying the t-test. Subgroup analysis based on the site will also be attempted.

AstraZeneca

University Health Network, Toronto

Digestive System Diseases

Recurrence

Microsatellite Instability

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Herbal and Botanical

Nivolumab

Daratumumab

Ipilimumab

Relatlimab

Immune Checkpoint Inhibitors

Cola

Cobimetinib

BMS-986016

Bristol-Myers Squibb

The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination with other anti-cancer drugs, will result in meaningful tumor size reduction, in participants with colon cancer that has come back or has spread, and who have a specific biomarker in their tumors.

A Study of Nivolumab Alone or Nivolumab Combination Therapy in Colon Cancer That Has Come Back or Has Spread

A Phase 2 Clinical Trial of Nivolumab, or Nivolumab Combinations in Recurrent and Metastatic Microsatellite Instability High (MSI-H) and Non-MSI-H Colon Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Basket Combination Study of Inhibitors of DNA Damage Response, Angiogenesis and Programmed Death Ligand 1 in Patients With Advanced Solid Tumors	NCT03851614	Mismatch Repair... Pancreatic Aden... Leiomyosarcoma	Durvalumab Olaparib Cediranib	18 Years -	University Health Network, Toronto
A Study of Nivolumab Alone or Nivolumab Combination Therapy in Colon Cancer That Has Come Back or Has Spread	NCT02060188	Microsatellite ... Microsatellite ... Mismatch Repair... Mismatch Repair...	Ipilimumab Nivolumab Cobimetinib Daratumumab BMS-986016	18 Years -	Bristol-Myers Squibb
Basket Combination Study of Inhibitors of DNA Damage Response, Angiogenesis and Programmed Death Ligand 1 in Patients With Advanced Solid Tumors	NCT03851614	Mismatch Repair... Pancreatic Aden... Leiomyosarcoma	Durvalumab Olaparib Cediranib	18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for mismatch repair proficient colorectal cancer