Clinical Trials /

Study of Azacitidine and Durvalumab in Advanced Solid Tumors

NCT02811497

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Azacitidine and Durvalumab in Advanced Solid Tumors
  • Official Title: An Open-label, Phase II Basket Study of a hypoMEThylating Agent Oral Azacitidine and DURvalumab (MEDI4736) (Anti-PDL1) in Advanced Solid Tumors (METADUR)

Clinical Trial IDs

  • ORG STUDY ID: METADUR-001
  • NCT ID: NCT02811497

Conditions

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

Interventions

DrugSynonymsArms
AzacitidineCC-486Azacitidine and Durvalumab
DurvalumabAzacitidine and Durvalumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Azacitidine and DurvalumabExperimentalAzacitidine 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.
  • Azacitidine
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  At least one measurable lesion according to RECIST v1.1.

          -  At least one lesion safely accessible for biopsy.

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion.

          -  Consent to provide archival tumor tissue (initial and subsequent tumor biopsy samples,
             if possible) for correlative biomarker studies, if available.

          -  Female subject of childbearing potential1 should have two negative pregnancy tests as
             verified by the investigator prior to starting any investigational product therapy

          -  Females of childbearing potential who are sexually active with a non-sterilized male
             partner must agree to practice true abstinence or use at least two effective methods
             of contraception for the study defined period.

          -  Non-sterilized males who are sexually active with a female partner of childbearing
             potential must agree to use at least two effective methods of contraception for the
             study defined period.

        Exclusion Criteria:

          -  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

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
             bleeding diatheses including any patient known to have evidence of acute or chronic
             hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
             illness/social situations that would limit compliance with study requirements or
             compromise the ability of the patient to give written informed consent

          -  Known history of previous clinical diagnosis of tuberculosis

          -  Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of investigational products.

          -  Female patients who are pregnant, breast-feeding or male or female patients of
             reproductive potential who are not employing an effective method of birth control.

          -  Irritable bowel syndrome or other serious gastrointestinal chronic conditions
             associated with diarrhea within the past 3 years prior to the start of treatment,
             and/or history of prior gastrectomy or upper bowel removal, or any other
             gastrointestinal disorder or defect that would interfere with the absorption,
             distribution, metabolism or excretion of the investigational product and/or predispose
             the patient to an increased risk of gastrointestinal toxicity.

          -  Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or
             cord compression.

          -  Patients with uncontrolled seizures.

          -  Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer
             treatment with the exception of patients on adjuvant endocrine therapy for a history
             of non-invasive breast cancer.

          -  Major surgery within 28 days prior to Day 1 of the study or still recovering from
             prior surgery.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results.

          -  Patients who are involuntarily incarcerated or are unable to willingly provide consent
             or are unable to comply with the protocol procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:4 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Control Rate (DCR)
Time Frame:16 weeks
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:5 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:
Measure:Incidence of treatment-emergent adverse events (AEs)
Time Frame:5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Health Network, Toronto

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