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

NCT02827838 | Terminated Early Phase 1 Results FDA Drug

• 4 other identifiers: IRB00038877NCI-2016-00639CCCWFU 60116P30CA012197
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stage III Oropharyngeal Squamous Cell Carcinoma; Human Papillomavirus Infection; Stage I Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (7)

• 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

  Up to 18 months

• 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.

  At baseline and at one week post treatment start

• 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-

  Up to 18 months

• 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

  Up to 18 months

• 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.

  Baseline and one week post treatment start

• 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).

  Up to 18 months

• 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-

  Up to 18 months

Secondary Outcomes (3)

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

  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

• Standardized Uptake Value (SUV) as Measured by PET Scans

  Up to 18 months

• Tumor Diameter Assessed Using RECIST Version 1.1 Criteria

  Up to 18 months

Study Arms (1)

Treatment (durvalumab, surgery)

EXPERIMENTAL

Patients 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.

Biological: Durvalumab; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (durvalumab, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (durvalumab, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (durvalumab, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck

Interventions

durvalumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Mercedes Porosnicu
• Organization: Wake Forest Baptist Comprehensive Cancer Center

mporosni@wakehealth.edu

336-716-8664

Study Officials

• Mercedes Porosnicu

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: July 11, 2016
• Study Start: January 1, 2017
• Primary Completion: April 22, 2022
• Study Completion: April 22, 2022
• Last Updated: March 17, 2025
• Results First Posted: March 17, 2025

Record last verified: 2025-02

Locations

US (1)