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Microsatellite Stable Colorectal CarcinomaPhase 2METADURNCT02811497

Study of Azacitidine and Durvalumab in Advanced Solid Tumors

A Phase 2 study testing Azacitidine and Durvalumab in people with Microsatellite Stable Colorectal Carcinoma and Platinum Resistant Epithelial Ovarian Cancer Type II, run by University Health Network, Toronto at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteCanada
Study dates
Sep 2016to 4 Aug 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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)

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.

Being tested
Azacitidine, Durvalumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02811497
Study groupRoleWhat they receive
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.
Receives: Drug: Azacitidine; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR)

    Measured: 4 weeks

Secondary outcomes (4)

  1. Disease Control Rate (DCR)

    Measured: 16 weeks

  2. Progression-free survival (PFS)

    Measured: 5 years

  3. Overall survival (OS)

    Measured: 5 years

  4. Incidence of treatment-emergent adverse events (AEs)

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2016 (estimated)
  2. Study startSep 2016
  3. Primary completion8 Nov 2018
  4. Study completion4 Aug 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02811497
Sponsor's protocol ID
METADUR-001
Acronym
METADUR
Status last verified
Mar 2021
First submitted
21 Jun 2016
Last updated
1 Apr 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32753546

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine and Durvalumab in people with Microsatellite Stable Colorectal Carcinoma and Platinum Resistant Epithelial Ovarian Cancer Type II, run by University Health Network, Toronto at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02811497, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.

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