Study of Azacitidine and Durvalumab in Advanced Solid Tumors

NCT02811497 | Completed Phase 2 DMC

• 1 other identifier: METADUR-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study of investigational drug, durvalumab given in combination with azacitidine (CC-486). The main purpose of this phase 2 study is to assess the antitumor activity of azacitidine in combination with durvalumab patients with microsatellite stable colorectal carcinoma (MSS-CRC), platinum resistant epithelial ovarian cancer type II (PR-OC), and estrogen receptor positive and HER2 negative breast cancer.

Conditions

Microsatellite Stable Colorectal Carcinoma; Platinum Resistant Epithelial Ovarian Cancer Type II; Estrogen Receptor Positive and HER2 Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  4 weeks

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  16 weeks

• Progression-free survival (PFS)

  5 years

• Overall survival (OS)

  5 years

• Incidence of treatment-emergent adverse events (AEs)

  5 years

Study Arms (1)

Azacitidine and Durvalumab

EXPERIMENTAL

Azacitidine will be given by mouth at a fixed dose of 300 mg daily for 14 consecutive days of every 28 day cycle for 3 cycles. Durvalumab will be given intravenously (by vein) at a fixed dose of 1500 mg (over 1 hour) on Day 1 of every 28 day cycle for 12 months or until disease progression.

Drug: Azacitidine; Drug: Durvalumab

Interventions

Azacitidine DRUG

Also known as: CC-486

Azacitidine and Durvalumab

Durvalumab DRUG

Azacitidine and Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent.
• Age ≥18 years or ≥20 years for Japanese participants.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥12 weeks
• Have histologically or cytologically-documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician.
• Have one of the following advanced (unresectable and/or metastatic) solid tumor indications:
• Microsatellite Stable Colorectal Carcinoma (MSS-CRC)
• Platinum Resistant Epithelial Ovarian Cancer Type II (PR-OC)
• Estrogen Receptor Positive and HER2 Negative Breast Cancer (ER+/HER2- BC):
• The following considerations will be made regarding prior treatment regimens:
• MSS-CRC: must have progressed or be intolerant of 5-FU, irinotecan, oxaliplatin and epidermal growth factor receptor (EGFR) mAb in patients with RAS wild type tumors, in recurrent/metastatic setting.
• PR-OC: must have progressed on at least 1, maximum of 2 lines of cytotoxic agents in the platinum resistant disease setting
• ER+/HER2- BC: must have progressed on at least 2, maximum of 5 lines of cytotoxic agents in recurrent/metastatic setting.
• Adequate normal organ and marrow function
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• Involvement in the planning and/or conduct of the study or previous enrolment in the present study.
• Participation in another clinical study with an investigational product during the last 28 days or 5 half-lives prior to study Day 1. Concurrent enrolment in an observational (noninterventional) clinical study or the follow-up period of an interventional study is allowed.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab. Prior anti-CTLA4 agents are allowed. Prior therapy with T-cell co-stimulatory agents (e.g. anti-CD137 antibody, anti-OX40 antibody) are allowed.
• Prior therapy with CC-486, azacitidine, decitabine or any other hypomethylating agent.
• History of another primary malignancy with exceptions.
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 28 days prior to the first dose of study drug (and within 6 weeks for nitrosourea or mitomycin C).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab with exceptions.
• Any unresolved toxicity CTCAE grade 2 from previous anti-cancer therapy.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1, with exception of chronic endocrinopathy that is stable on hormone replacement.
• Active or prior documented autoimmune disease within the past 2 years.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency
• History of allogeneic organ transplant
• History of hypersensitivity to study drug formulations, including azacitidine, mannitol, or durvalumab, its constituents, or to any other humanized monoclonal antibody

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Taylor K, Loo Yau H, Chakravarthy A, Wang B, Shen SY, Ettayebi I, Ishak CA, Bedard PL, Abdul Razak A, R Hansen A, Spreafico A, Cescon D, Butler MO, Oza AM, Lheureux S, Stjepanovic N, Van As B, Boross-Harmer S, Wang L, Pugh TJ, Ohashi PS, Siu LL, De Carvalho DD. An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors. J Immunother Cancer. 2020 Aug;8(2):e000883. doi: 10.1136/jitc-2020-000883.

  PMID: 32753546 DERIVED

MeSH Terms

Interventions

Azacitidine; cc-486; durvalumab

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Lillian Siu, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2016
• First Posted: June 23, 2016
• Study Start: September 1, 2016
• Primary Completion: November 8, 2018
• Study Completion: August 4, 2020
• Last Updated: April 1, 2021

Record last verified: 2021-03

Locations

CA (1)