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A Multi-Cancer, Multi-State, Platform Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck to Correlate Clinical, Molecular and Immunologic Parameters With DNA Methylation (DOME)

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ClinicalTrials.gov Identifier: NCT04262388
Recruitment Status : Withdrawn (Overall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet.)
First Posted : February 10, 2020
Last Update Posted : November 17, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE February 5, 2020
First Posted Date  ICMJE February 10, 2020
Last Update Posted Date November 17, 2020
Estimated Study Start Date  ICMJE January 2021
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • cfMeDIP-seq-based assays of blood samples collected serially on study. Association between cfMeDIP and Toxicity (defined as ≥ Grade 2 immune- adverse event (AE) as per CTCAE 5.0) [ Time Frame: 2 years ]
    Identify cfMeDIP-seq-based predictive signature(s) that are correlated with specific outcome to durvalumab and oleclumab such as response/resistance or occurrence of toxicity in pancreatic ductal adenocarcinoma (PDAC), non-small-cell carcinoma (NSCLC) and squamous cell carcinoma of head and neck (SCCHN).
  • Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: 2 years ]
  • Disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: 2 years ]
  • Duration of response (DoR) [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
  • Incidence of treatment-emergent adverse events (AEs) [ Time Frame: 2 years ]
    To assess the safety and tolerability of durvalumab and oleclumab in specific disease states in PDAC, NSCLC and SCCHN
  • Overall survival (OS) [ Time Frame: 2 years ]
  • Relapse-free survival (RFS) [ Time Frame: 2 years ]
  • Progression-free survival (PFS) [ Time Frame: 2 years ]
  • Pathological response rate in "Window" cohorts [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multi-Cancer, Multi-State, Platform Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck to Correlate Clinical, Molecular and Immunologic Parameters With DNA Methylation
Official Title  ICMJE A Multi-Cancer, Multi-State, Platform Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck to Correlate Clinical, Molecular and Immunologic Parameters With DNA Methylation (DOME)
Brief Summary

This is a phase II, single center, open label, multi-cohort platform study to identify a signature in tumor tissues, blood or stool that might help identify participants who are more likely to experience tumor shrinkage or side effects from the combination of the study drugs durvalumab and oleclumab. In addition, this study will see if participants with certain types of advanced cancer benefit from the experimental drug combination of durvalumab and oleclumab, will evaluate the safety and tolerability of durvalumab and oleclumab, and to understand the effects that durvalumab and oleclumab have at a molecular level in tumor cells and their effects on the immune system. This study will look at subjects with locally advanced or recurrent/metastatic pancreatic ductal adenocarcinoma (PDAC), non-small-cell carcinoma (NSCLC) and squamous cell carcinoma of head and neck (SCCHN).

Within each cancer type, 40 patients will be enrolled (for a total of 120 patients on study): 20 patients will be enrolled with locally advanced disease ("window") and treated with durvalumab 1500 mg given by IV x 1 dose and oleclumab 3000 mg x 2 doses every 2 weeks prior to definitive therapy (e.g. surgery), and 20 patients will be enrolled with recurrent/metastatic ("metastatic") disease and treated with durvalumab 1500 mg given by IV every 4 weeks and oleclumab 3000 mg given by IV every 2 weeks x 4 doses then IV every 4 weeks till disease progression, toxicity, withdrawal of subject consent, or another discontinuation reason. For locally advanced PDAC patients, approximately 10 of the 20 subjects may receive 6-8 cycles of modified FOLFIRINOX (mFFX) prior to the administration of durvalumab and oleclumab.

Detailed Description The study hypothesis is that the combination of oleclumab (anti-cluster of differentiation [CD]73) with durvalumab (anti programmed cell death ligand 1 [PD-L1]) will demonstrate adequate safety, tolerability, and antitumor activity in subjects with locally advanced or recurrent/metastatic: pancreatic ductal adenocarcinoma (PDAC), non-small-cell lung cancer (NSCLC) and squamous cell carcinoma of head and neck (SCCHN), and that circulating free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) can yield cancer type-agnostic predictive biomarker(s) of response and/or toxicity in subjects receiving this combination.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Ductal Adenocarcinoma
  • Non-small Cell Lung Cancer
  • Squamous Cell Carcinoma of Head and Neck
Intervention  ICMJE
  • Biological: Durvalumab
    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.
    Other Name: IMFINZI
  • Biological: Oleclumab
    Oleclumab is a human immunoglobulin G1 lambda monoclonal antibody (mAb) with a triple mutation in the heavy chain constant region for reduced effector function. Oleclumab selectively binds to cluster of differentiation 73 (ecto-5'-nucleotidase) (CD73) and inhibits CD73-associated ectonucleotidase activity, thereby inhibiting the CD73-mediated production of immunosuppressive adenosine. Extracellular adenosine contributes to the immunosuppressive effects of both regulatory T cells and myeloid derived suppressor cells, among others. This, in turn, leads to increased antitumor immunity.
Study Arms  ICMJE
  • Experimental: Window
    Within each cancer type, 40 patients will be enrolled (for a total of 120 patients on study): 20 patients will be enrolled with locally advanced disease ("window") and treated with durvalumab 1500 mg given by IV x 1 dose and oleclumab 3000 mg x 2 doses every 2 weeks prior to definitive therapy (e.g. surgery).
    Interventions:
    • Biological: Durvalumab
    • Biological: Oleclumab
  • Experimental: Metastatic
    Within each cancer type, 40 patients will be enrolled (for a total of 120 patients on study): 20 patients will be enrolled with recurrent/metastatic ("metastatic") disease and treated with durvalumab 1500 mg given by IV every 4 weeks and oleclumab 3000 mg given by IV every 2 weeks x 4 doses then IV every 4 weeks till disease progression, toxicity, withdrawal of subject consent, or another discontinuation reason.
    Interventions:
    • Biological: Durvalumab
    • Biological: Oleclumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: November 13, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: February 7, 2020)
120
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date January 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18 years at the time of screening or age of consent
  2. Written informed consent and any locally required authorization (eg, data privacy) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  3. ECOG of 0 or 1
  4. Weight ≥ 35 kg
  5. Must have a life expectancy of at least 12 weeeks
  6. Histological or cytological confirmation
  7. At least 1 measurable lesion according to RECIST version 1.1
  8. Archival tumor formalin-fixed, paraffin-embedded (FFPE) specimens for correlative biomarker studies are required (1 H&E and 15 unstained slides) unless no such sample is available or insufficient sample exists. Subjects with insufficient archived tumor samples are still eligible
  9. Adequate organ and marrow function
  10. Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening to 180 days after the final dose of study treatment
  11. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from screening to 180 days after receipt of the final dose of study treatment

Exclusion Criteria:

  1. Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment.
  2. Prior receipt of any immune-mediated therapy
  3. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
  4. Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
  5. Subjects with a history of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms
  6. Subjects with prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment
  7. Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment
  8. HIV, Hep A, B, or C
  9. History of primary immunodeficiency, solid organ transplantation, or active tuberculosis
  10. Other invasive malignancy within 2 years
  11. Known allergy or hypersensitivity to investigational product formulations
  12. History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment
  13. Active grade 3 or greater edema
  14. Uncontrolled intercurrent illness
  15. Any history of leptomeningeal disease or cord compression
  16. Untreated CNS metastatic disease.
  17. Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment.
  18. Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment
  19. Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery
  20. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
  21. Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures
  22. Any condition that, in the opinion of the investigator, would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04262388
Other Study ID Numbers  ICMJE DOME
19-6280 ( Other Identifier: University Health Network )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Lillian Siu, MD Princess Margaret Cancer Centre
PRS Account University Health Network, Toronto
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP