AzTrials
AzTrials

Squamous Cell Carcinoma, Head And NeckPhase 1PRIMED-001NCT02993991

Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity

A Phase 1 study testing Mocetinostat and Durvalumab in people with Squamous Cell Carcinoma, Head And Neck and Squamous Cell Carcinoma Mouth, run by University Health Network, Toronto at 1 site in Canada.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This is a Phase 1 Window of Opportunity study to evaluate the pharmacodynamic and immune effects of pre-operative therapy with Mocetinostat and Durvalumab on patients with squamous cell carcinoma of the oral cavity. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Mocetinostat and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteCanada
Study dates
10 Oct 2017to 21 Dec 2017
Phase
Phase 1
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

  • Signed written and voluntary informed consent.
  • Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
  • Age > 18 years, male or female. Disease characteristics
  • Patient must be diagnosed with histologically confirmed squamous cell carcinoma of the oral cavity (SCCOC) (floor of mouth, anterior 2/3 tongue, buccal mucosa, upper and lower gingiva, and retromolar trigone) considered resectable by the head and neck surgical rounds (T2-4a, N0-2, M0; without evidence of distant metastasis).
  • Patient must be willing and able to provide up to 2 fresh tumor biopsies for histopathological and biomarker evaluation; first as pre-treatment baseline, and the second after treatment with mocetinostat but prior to treatment with durvalumab.
  • Patients who decline an in-house fresh pre-treatment tumor biopsy must give consent to provide a tumor block from an existing diagnostic primary tumor biopsy completed within 90 days of enrollment, which is of acceptable quality and quantity for analysis, as assessed by the study site correlatives team.
Show all 19Show fewer
  • No anti-neoplastic treatment is allowed between the time from obtaining baseline tumor specimen and enrollment.
  • Patient characteristics
  • ECOG performance status 0-1.
  • Patient must have adequate organ function as determined by the following:
  • Renal function: i. Serum creatinine < 1.5 ULN (upper limit of normal range) or a calculated creatinine clearance of > 50mL/min using the following formula: Creatinine clearance = [(140-age) x wt (kg) x Constant*] / creatinine (umol/L)
  • Constant = 1.23 for men, and 1.04 for women
  • Bone marrow function (without hematopoietic growth factors or transfusion): i. Absolute neutrophil count (ANC) > 1.5 x 109/L ii. Leukocytes > 3.0 x 109/L iii. Hemoglobin > 90 g/L or > 9g/dL iv. Platelets > 100 x 109/L
  • Liver function: i. Total bilirubin < ULN ii. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < 2.5 x ULN
  • Cardiac function: i. A normal left ventricular ejection fraction (LVEF) of > 50% and the absence of any clinically significant pericardial effusion, as evidenced by an echocardiogram performed within 4 weeks of the study commencement.
  • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Subject is 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.

Who cannot join

  • Primary site of head and neck carcinoma unknown, lip, hard palate, skin, or outside the oral cavity.
  • Patients with tumors that invade major vessels, as shown unequivocally by imaging studies.
  • For patients with tumors that do not invade major blood vessels but are within 3mm of the carotid artery or branches thereof, any anticoagulant therapy (including aspirin, non-steroidal anti-inflammatories, antiplatelet agents or other anti-coagulants) must be discontinued.
  • Patients with any prior history of bleeding related to the current head and neck cancer.
  • Patients with a history of gross hemoptysis (bright red blood of ½ teaspoon or more per episode of coughing) < 3 months prior to enrollment.
  • Prior or concurrent radiation therapy to tumor at site of planned resection.
Show all 33Show fewer
  • Any concurrent chemotherapy, biologic, immunologic or hormonal therapy for cancer treatment.
  • Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
  • Current or prior use of immunosuppressive medication within 14 days prior to starting dosing. The following are exceptions to this criteria:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
  • Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or equivalent.
  • Steroids as premedication for hypersensitivity reactions (eg, computed tomography scan premedication).
  • Active or documented history of autoimmune disease within 2 years before screening, including:
  • Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis).
  • Patients with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment within the past 2 years, are not excluded.
  • History of primary immune deficiency.
  • History of organ transplant that requires use of immunosuppressive medications.
  • Use of any live vaccines against infectious diseases within 4 weeks of study treatment initiation.
  • Known allergy or reaction to any component of Mocetinostat and/or Durvalumab formulation.
  • Known history of tuberculosis.
  • Subjects who are known to be human immunodeficiency (HIV) positive.
  • Subjects who are known to be hepatitis B or C positive.
  • Female patients who are pregnant or breast-feeding.
  • Male or female patients of reproductive potential who are not willing to use effective birth control from screening to 180 days following the last dose of durvalumab.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from Mocetinostat or Durvalumab, or compromise the ability of the subject to give written informed consent.
  • Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
  • History of another primary malignancy, except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence,
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease,
  • Adequately treated carcinoma in situ without evidence of disease.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medications.
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.

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

This is a Phase 1 Window of Opportunity study to evaluate the pharmacodynamic and immune effects of pre-operative therapy with Mocetinostat and Durvalumab on patients with squamous cell carcinoma of the oral cavity.

Read the detailed description

This is a single center, open-label, non-randomized, pre-operative window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative Mocetinostat and Durvalumab.

This study will involve treatment with Mocetinostat and Durvalumab, tests and procedures done for safety and the collection of blood samples for biomarker research. Tissue samples (fresh biopsy or archival tissue) will also be collected for biomarker research and evaluation.

Being tested
Mocetinostat, Durvalumab
Medical subject headings
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.

  • MocetinostatDrug

    Also called MGCD0103

    Mocetinostat (MGCD0103) is a potent small molecule HDAC inhibitor that targets human HDAC isoforms. It is an orally bioavailable, second generation benzamide inhibitor of HDAC 1, 2, 3 and 11 with broad spectrum antitumor activity in vitro and in vivo.

  • DurvalumabBiological

    Also called MEDI4736

    Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against human PD-L1. It is selective for recombinant PD-L1 and blocks the binding of recombinant PD-L1 to the PD-1 and CD80 receptors.

Study groups in NCT02993991
Study groupRoleWhat they receive
Mocetinostat and DurvalumabExperimentalPatients will start therapy with mocetinostat within 10 days of study enrollment. Mocetinostat will be given in 2 dose levels (n = 6 evaluable patients each) of 70mg three-times weekly and 90mg three-times weekly for 2 weeks. Durvalumab will be given as a single infusion at a dose of 1500mg, over a period of 1-hour, on day 8 of the study.
Receives: Drug: Mocetinostat; Biological: Durvalumab

What is being measured

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

  1. Pharmacodynamic effects with biomarker analyses (Tumor PD-L1 by IHC; Density of peri-tumoral and intra-tumoral CD3, CD4 and CD8-positive lymphocytes; Serum pro-inflammatory cytokines and chemokines)

    Measured: 3 years

  2. Immune effects with biomarker analyses (Tumor PD-L1 by IHC; Density of peri-tumoral and intra-tumoral CD3, CD4 and CD8-positive lymphocytes; Serum pro-inflammatory cytokines and chemokines)

    Measured: 3 years

Secondary outcomes (6)

  1. Toxicities as per NCI CTCAE v4.1

    Measured: 3 years

  2. Rate of completion of surgery within the initially planned window as per RECIST v1.1

    Measured: 3 years

  3. Rate of disease progression as per RECIST v1.1 during the pre-operative treatment period

    Measured: 3 years

  4. Rate of post-operative complications as per NCI CTCAE v4.1

    Measured: 3 years

  5. Optimal biologically active dose of mocetinostat (Correlation of tumor and serum-based assessments with mocetinostat dose levels)

    Measured: 3 years

  6. Changes in serum mocetinostat concentrations prior to and following durvalumab therapy

    Measured: 3 years

Timeline

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

  1. First posted15 Dec 2016 (estimated)
  2. Study start10 Oct 2017 (estimated)
  3. Primary completion21 Dec 2017
  4. Study completion21 Dec 2017

Why it stopped: The study has been terminated due to a change in internal prioritization and not due to any safety concerns.

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02993991
Sponsor's protocol ID
PRIMED-001
Acronym
PRIMED-001
Status last verified
Dec 2017
First submitted
1 Dec 2016
Last updated
29 Dec 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Mocetinostat and Durvalumab in people with Squamous Cell Carcinoma, Head And Neck and Squamous Cell Carcinoma Mouth, 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 19 inclusion and 33 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 29 Dec 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Pharmacodynamic effects with biomarker analyses (Tumor PD-L1 by IHC; Density of peri-tumoral and intra-tumoral CD3, CD4 and CD8-positive lymphocytes; Serum pro-inflammatory cytokines and chemokines) (time frame: 3 years). The study lists 2 primary outcomes in all. 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 NCT02993991.

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 29 Dec 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in