Pancreatic Ductal AdenocarcinomaPhase 2DOMENCT04262388
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
A Phase 2 study testing Durvalumab and Oleclumab in people with Pancreatic Ductal Adenocarcinoma and Non-small Cell Lung Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Ductal Adenocarcinoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck
- What is being tested?
- Durvalumab and Oleclumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2021to Jan 2023
- 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
- Age ≥ 18 years at the time of screening or age of consent
- 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
- ECOG of 0 or 1
- Weight ≥ 35 kg
- Must have a life expectancy of at least 12 weeeks
- Histological or cytological confirmation
Show all 11Show fewer
- At least 1 measurable lesion according to RECIST version 1.1
- 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
- Adequate organ and marrow function
- 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
- 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
Who cannot join
- 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.
- Prior receipt of any immune-mediated therapy
- Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
- Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
- 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
- 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
Show all 22Show fewer
- Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment
- HIV, Hep A, B, or C
- History of primary immunodeficiency, solid organ transplantation, or active tuberculosis
- Other invasive malignancy within 2 years
- Known allergy or hypersensitivity to investigational product formulations
- History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment
- Active grade 3 or greater edema
- Uncontrolled intercurrent illness
- Any history of leptomeningeal disease or cord compression
- Untreated CNS metastatic disease.
- Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment.
- Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment
- Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery
- Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
- Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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)
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.
Read the 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.
- Conditions
- Pancreatic Ductal Adenocarcinoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck
- Being tested
- Durvalumab, Oleclumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabBiological
Also called IMFINZI
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.
OleclumabBiological
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 group | Role | What they receive |
|---|---|---|
| Window | Experimental | 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). Receives: Biological: Durvalumab; Biological: Oleclumab |
| Metastatic | Experimental | 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. Receives: Biological: Durvalumab; Biological: Oleclumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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).
Measured: 2 years
Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 2 years
Disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: 2 years
Duration of response (DoR)
Measured: 2 years
Secondary outcomes (5)
Incidence of treatment-emergent adverse events (AEs)
To assess the safety and tolerability of durvalumab and oleclumab in specific disease states in PDAC, NSCLC and SCCHN
Measured: 2 years
Overall survival (OS)
Measured: 2 years
Relapse-free survival (RFS)
Measured: 2 years
Progression-free survival (PFS)
Measured: 2 years
Pathological response rate in "Window" cohorts
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study startJan 2021 (estimated)
- Primary completionJan 2023 (estimated)
- Study completionJan 2023 (estimated)
Why it stopped: Overall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Lillian Siu, MD, Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04262388
- Sponsor's protocol ID
- DOME
- Other IDs
- 19-6280
- Acronym
- DOME
- Status last verified
- Nov 2020
- First submitted
- 5 Feb 2020
- Last updated
- 17 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04262388
- Acronym / sponsor ID
- DOME / DOME
- Conditions
- Pancreatic Ductal Adenocarcinoma, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Overall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Jan 2021 (estimated)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Jan 2023 (estimated)
- First posted
- 10 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Window | Experimental | Biological: Durvalumab, Biological: OleclumabWithin 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). |
| Metastatic | Experimental | Biological: Durvalumab, Biological: OleclumabWithin 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years at the time of screening or age of consent
- 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
- ECOG of 0 or 1
- Weight ≥ 35 kg
- Must have a life expectancy of at least 12 weeeks
Key exclusion criteria (22 listed)
- 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.
- Prior receipt of any immune-mediated therapy
- Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
- Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: IMFINZIDurvalumab 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. | Biological | Metastatic, Window |
| OleclumabOleclumab 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. | Biological | Metastatic, Window |
Primary outcome
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
5 secondary outcomes
Incidence of treatment-emergent adverse events (AEs)
Time frame: 2 years
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lillian Siu, MD principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab and Oleclumab in people with Pancreatic Ductal Adenocarcinoma and Non-small Cell Lung Cancer, 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 11 inclusion and 22 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: withdrawn, as of the sponsor's last update on 17 Nov 2020. 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 was withdrawn before enrolling participants, so there are no results.
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?
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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Nov 2020; AzTrials last refreshed its copy on 6 Nov 2026.