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Human Papillomavirus InfectionEarly Phase 1NCT02827838

Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer

A Early Phase 1 study testing Durvalumab, Laboratory Biomarker Analysis and Therapeutic Conventional Surgery in people with Human Papillomavirus Infection and Stage I Oral Cavity Squamous Cell Carcinoma, run by Wake Forest University Health Sciences at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This pilot clinical trial studies how well durvalumab before surgery works in treating patients with oral cavity or oropharynx cancer. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab, Laboratory Biomarker Analysis and Therapeutic Conventional Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
Jan 2017to 22 Apr 2022
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically or cytologically confirmed HNSCC of the oral cavity (OC; more than 90% patients have HPV negative cancer) or oropharynx (about 60-80% of patient have HPV positive cancer)
  • Presence of radiologically of clinically documented disease. All radiology studies must be performed within 28 days prior to registration
  • Any stage, considered candidates for surgery and planned for surgery either by robotic or by standard surgical technique
  • Documentation of HPV tested by polymerase chain reaction (PCR) (resulted or pending)
  • Willing to provide consent for an additional tissue biopsy for research purposes, to allow a part of their surgical tumor tissue to be utilized for research (in case tumor tissue has not already been saved in the tumor tissue bank), and to donate samples of blood and saliva collected weekly through the treatment
  • All patients must have provided informed consent for correlative studies
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Patients must have no prior exposure to immune-mediated therapy, including anti- cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1, anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines
  • At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as > or = 10 mm in the longest diameter (except lymph nodes, which must have a short axis > or = 15 mm) with CT or magnetic resonance imaging (MRI) or clinical measurement and that is suitable for accurate repeated measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines
  • Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of registration, and that wound healing has occurred
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9.0 g/dL
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN) (institutional upper limit of normal)
  • Total bilirubin is less than or equal to ULN, except the case in which the elevated total bilirubin is not a sign of liver disease, such as the Gilbert Syndrome, in which case a Total Bilirubin less than or equal to 2X ULN is acceptable.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
  • Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: >= 60 years old and no menses for >= 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
  • In accordance with National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) policy, protocol treatment is to begin within 2 working days of patient registration
  • Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of American [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  • Age 18 years or older at time of study entry.
  • 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

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study
  • Participation in another clinical study with an investigational product during the last 6 months (mo)
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  • Receipt of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within the last 6 mo (before the first dose of Durvalumab).
  • Mean QT interval corrected for heart rate (corrected QT [QTc]) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correction
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
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  • Any unresolved toxicity (> Common Terminology Criteria for Adverse Events [CTCAE] grade 2) from previous anti-cancer therapy; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
  • Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1
  • Active or prior documented autoimmune disease within the past 2 years; NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  • 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 durvalumab or any excipient
  • 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 subject 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 subject 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 receiving durvalumab
  • Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
  • Patients with body weight <= 30 kg
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Comprehensive Cancer Center of Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Pilot Study to Evaluate the Anti-Tumor Effect of Durvalumab (Medi4736) in Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN), Human Papilloma Virus (HPV) Positive Versus Negative, When Treated Before Surgery

This pilot clinical trial studies how well durvalumab before surgery works in treating patients with oral cavity or oropharynx cancer. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate the effect of durvalumab on local and systemic immune activation by HPV status in patients with oral cavity and oropharynx head and neck squamous cell carcinoma (HNSCC).

II. To examine the effects of durvalumab on systemic immune response to HPV and tumor associated antigens.

III. To examine the effects of durvalumab on immune regulatory mechanisms. IV. To explore the association between levels of immune-regulatory micro-ribonucleic acid (miR) in plasma and saliva and immune response.

SECONDARY OBJECTIVES:

  1. Investigate the effect of the treatment with durvalumab on the computed tomography (CT) scan and positron emission tomography (PET) scan response.

II. Evaluate the safety of a short induction treatment with durvalumab.

OUTLINE:

Patients receive durvalumab intravenously (IV) over approximately 60 minutes on day 1. Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab, patients undergo surgery. Patients may receive an additional dose of durvalumab if time to surgery is longer than 30 days.

After completion of study treatment, patients are followed up for 90 days.

Being tested
Durvalumab, Laboratory Biomarker Analysis, Therapeutic Conventional Surgery
Medical subject headings
Papillomavirus Infections, 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 Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgery

Study groups in NCT02827838
Study groupRoleWhat they receive
Treatment (durvalumab, surgery)ExperimentalPatients receive durvalumab IV over approximately 60 minutes on day 1. Treatment repeats every 2 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 3-17 days after last dose administration of durvalumab, patients undergo surgery. Patients may receive an additional dose of durvalumab if time to surgery is longer than 30 days.
Receives: Biological: Durvalumab; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Immune Effector Assessed in Blood by Flow Cytometry and in Tissue by Immunohistochemistry

    Concentration of certain immune effector will be assessed in blood pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. Tumor-infiltrating immune-regulator and effector cells will be quantified (0 to 3+) using standing immunofluorescence techniques. Counts and percents will be calculated for these measures overall and by HPV (+/-) groups pre- and post-treatment. Fisher exact tests will be used to compare groups at pre- and post- treatment. Stuart-Maxwell tests (generalizations of the McNemar's Test

    Measured: Up to 18 months

  2. Immune-regulatory miR Responses as Measured in Plasma Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR)

    Percent change of levels of immune-regulatory miRs assessed in plasma assessed pre-treatment and one week post-treatment.

    Measured: At baseline and at one week post treatment start

  3. Systemic Immune Response to HPV Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

    Lab results will be compared between patients who are HPV+ and HPV- using 2 sample t-tests. These measures will be compared in several ways. First, baseline, pre-treatment levels will be examined using descriptive statistics (n, mean, standard deviations, range). These measures will be examined overall and by HPV (+/-) groups. For each measure, and time point, 95% confidence intervals will be estimated. Next, two sample t-tests will be performed to compare levels of the measures at baseline. Next, measures taken post-treatment will be examined in a similar manner (descriptive statistics and 2-

    Measured: Up to 18 months

  4. Regulatory Responses Assessed in Blood by Flow Cytometry and in Tissue by Immunohistochemistry

    Concentration of certain regulatory cells will be assessed in blood pre- and post- treatment. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. Tumor-infiltrating immune-regulator and effector cells will be quantified (0 to 3+) using standing immunofluorescence techniques. Counts and percents will be calculated for these measures overall and by HPV (+/-) groups pre- and post-treatment. Fisher exact tests will be used to compare groups at pre- and post- treatment. Stuart-Maxwell tests (generalizations of the McNemar's Tes

    Measured: Up to 18 months

  5. Immune-regulatory miR Responses as Measured in Saliva Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR)

    Percent change of levels of immune-regulatory miRs assessed in saliva assessed pre-treatment and one week post-treatment.

    Measured: Baseline and one week post treatment start

  6. Immune-regulatory miR Responses as Measured in Tumor Tissue Assessed by Quantitative Reverse Transcriptase PCR (qRT-PCR)

    Levels of immune-regulatory miRs assessed in blood, saliva and tumor tissue will be assessed pre- and post- treatments. Descriptive statistics, confidence intervals will be calculated and 2-sample t-tests will be performed. In addition, correlations between the different methods will be examined (i.e., correlation between saliva and blood measures, saliva and tumor measures, and blood and tumor measures).

    Measured: Up to 18 months

  7. Systemic Immune Response to Tumor Associated Antigens Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

    Lab results will be compared between patients who are HPV+ and HPV- using 2 sample t-tests. These measures will be compared in several ways. First, baseline, pre-treatment levels will be examined using descriptive statistics (n, mean, standard deviations, range). These measures will be examined overall and by HPV (+/-) groups. For each measure, and time point, 95% confidence intervals will be estimated. Next, two sample t-tests will be performed to compare levels of the measures at baseline. Next, measures taken post-treatment will be examined in a similar manner (descriptive statistics and 2-

    Measured: Up to 18 months

Secondary outcomes (3)

  1. Incidence of Adverse Events (AEs) as Measured by CTCAE Version 4.03

    AEs will be coded using the Medical Dictionary for Regulatory Activities to their organ class by preferred term. Coded AEs will be displayed by frequency, severity, and relationship to treatment (durvalumab) in the safety population. In addition, summary tables will be generated for the following situations: 1) fatigue, diarrhea, nausea and skin rash; 2) Immune-mediated reactions of any grade; 3) other adverse events graded as 3 or more by CTCAE Version 4.03; 4) Durvalumab dose reductions; 5) discontinuations of treatment with durvalumab, with specification of reason for discontinuation; and 6) changes in the surgical treatment schedule. Toxicity grades Grade I (mild), Grade II (moderate), Grade III (severe), Grade IV (life threatening) and Grade V (fatal). Toxicities of greater than or equal to Grade III (except infusion reaction) are considered worse outcomes.

    Measured: At baseline (pre-treatment), during scheduled treatment and up to the 90-day follow up period after the last dose of study drug administered, with a median of 1 month and maximum of 13 months

  2. Standardized Uptake Value (SUV) as Measured by PET Scans

    Change in SUV activity as measured by PET scans from baseline to post-treatment not specific to HPV status.

    Measured: Up to 18 months

  3. Tumor Diameter Assessed Using RECIST Version 1.1 Criteria

    Change in tumor diameters will be compared between groups (HPV +/-) pre- and post- treatment.

    Measured: Up to 18 months

Timeline

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

  1. First posted11 Jul 2016 (estimated)
  2. Study startJan 2017
  3. Primary completion22 Apr 2022
  4. Study completion22 Apr 2022

Why it stopped: Study closed prior to meeting enrollment goal and funding issues

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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02827838
Sponsor's protocol ID
IRB00038877
Other IDs
NCI-2016-00639, CCCWFU 60116, P30CA012197
Status last verified
Feb 2025
First submitted
20 May 2016
Last updated
17 Mar 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Durvalumab, Laboratory Biomarker Analysis and Therapeutic Conventional Surgery in people with Human Papillomavirus Infection and Stage I Oral Cavity Squamous Cell Carcinoma, run by Wake Forest University Health Sciences at 1 site in United States.

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 19 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: stopped early, as of the sponsor's last update on 17 Mar 2025. 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 United States. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Immune Effector Assessed in Blood by Flow Cytometry and in Tissue by Immunohistochemistry (time frame: Up to 18 months). The study lists 7 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 NCT02827838.

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 Mar 2025.

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