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Squamous Cell Carcinoma of the Head and NeckPhase 1NCT03635164

Radiotherapy With Durvalumab Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma

A Phase 1 study testing Durvalumab and Stereotactic Body Radiation Therapy (SBRT) in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Colorado, Denver at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment must be diagnosed with non-metastatic, biopsy-proven stage II-IVB oral cavity, stage III-IVB larynx and hypopharynx, or stage III-IVB HPV/p16 negative intermediate-high risk oropharynx head and neck cancer, and… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab and Stereotactic Body Radiation Therapy (SBRT)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
3 sitesUnited States
Study dates
12 Nov 2018to 2 May 2023
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

  • Histologically or cytologically confirmed: stage II-IVB oral cavity, stage III-IVB larynx, stage III-IVB hypopharynx, or stage III-IVB HPV and/or p16 negative intermediate-high risk oropharynx head and neck cancer (AJCC 8th edition)
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm by CT, PET/CT or MRI or >10 mm on visual inspection by clinical exam
  • Patients who are deemed resectable by ENT surgeon without pre-existing medical conditions that could inhibit surgery following neoadjuvant therapy, and do not refuse surgery
  • Written informed consent and HIPAA authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
  • Age > 18 years at time of study entry
  • ECOG performance status ≤ 1
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  • Life expectancy ≥ 24 weeks
  • Body weight >30kg
  • Adequate normal organ and marrow function as defined below:
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count (ANC) 1.0 x 109/L (> 1000 per mm3)
  • Platelet count ≥75 x 109/L (>75,000 per mm3)
  • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
  • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  • Males:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
  • Females:
  • Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85
  • 72 x serum creatinine (mg/dL)
  • 10. 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 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).
  • 11. Patient 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

  • Participation in another clinical study with an investigational product during the last 3 months
  • Patients with active ILD / pneumonitis or with a history of ILD/ pneumonitis requiring steroids
  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 30 days prior to the first dose of study drug for patients who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C. (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)
  • Patients with QTc interval > 470 msec during screening
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  • Current or prior use of immunosuppressive medication within 14 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. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy that is not part of standard NCCN indicated HNSCC adjuvant concurrent CRT. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • History of allogenic organ or bone marrow transplantation
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of IP 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
  • History of leptomeningeal carcinomatosis
  • History of active primary immunodeficiency
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 90 days after the last dose of durvalumab monotherapy. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  • Prior randomisation or treatment in a previous durvalumab clinical study
  • Patients with p16-positive oropharyngeal SCCA. No verification of p16 status is needed for laryngeal cancer or oral cavity cancer.
  • Patients with sinonasal SCCAs
  • Patients with metastatic SCCA neck disease with an unknown primary tumor site
  • Patients with distant metastatic disease on initial screening imaging
  • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

Other trials in United States

About this study

Official title: Phase I/Ib Trial of Radiotherapy in Combination With Durvalumab (MEDI4736) Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma of the Head and Neck (HNSCC)

This is a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment must be diagnosed with non-metastatic, biopsy-proven stage II-IVB oral cavity, stage III-IVB larynx and hypopharynx, or stage III-IVB HPV/p16 negative intermediate-high risk oropharynx head and neck cancer, and must be eligible and amenable to surgical resection.

Read the detailed description

This study will be enrolled using a 3+3 model. Patients will receive one dose of neoadjuvant durvalumab 1500 mg approximately 3-6 weeks prior to standard of care surgery. It will be given concurrently with the first dose of radiation (RT). The starting RT dose level will be given as 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease (Table 1) only to minimize exposure to normal tissue. If toxicity develops and surgery is delayed by more than 8 weeks (qualifying as a DLT), the radiation dose will be dropped per protocol for the next set of patients. If this dose is tolerated, the dose will be increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients. Patients will proceed to surgical resection approximately 3-6 weeks after radiation as recommended by the ENT surgeon.

Being tested
Durvalumab, Stereotactic Body Radiation Therapy (SBRT), Standard of Care Therapy
Keywords
HPV Negative, Durvalumab, Surgical Resection, Neoadjuvant, Radiation
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.

  • DurvalumabDrug

    Patients will receive one dose of neoadjuvant durvalumab 1500 mg approximately 3-6 weeks prior to standard of care surgery. It will be given concurrently with the first dose of radiation (RT). Patients will receive up to six doses of durvalumab and radiation post-operatively.

  • Stereotactic Body Radiation Therapy (SBRT)Radiation

    The starting RT dose level will be given as 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease only to minimize exposure to normal tissue. If toxicity develops and surgery is delayed by more than 8 weeks (qualifying as a DLT), the radiation dose will be dropped per protocol for the next set of patients. If this dose is tolerated, the dose will be increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients.

  • Standard of Care TherapyProcedure or surgery

    Patients will proceed to surgical resection 3-6 weeks after radiation as recommended by the ENT surgeon.

Study groups in NCT03635164
Study groupRoleWhat they receive
Dose Escalation and ExpansionExperimentalPart 1 of this trial will use a traditional 3+3 design will be used for this trial (i.e. cohort sizes of 3 patients for the first and second cohort at each dose level). Dose escalation will occur as long as there are minimal dose limiting toxicities.The expectation is that 9 patients will be enrolled to the trial during part 1.This is based on the expectation that all dose levels are safe (i.e. patients will not experience DLTs at all dose levels). The range of patients needed will be 6-12 patients. Part 2 of this trial will be an expansion cohort. A total of 8 additional patients will be enrolled at the dose level determined to be the MTD in part 1 of the study. These 8 patients will be used to confirm that the MTD is a safe combination, as well as provide additional patients to investigate the efficacy for the treatment combination. Note: Standard of care surgery will follow 3-6 weeks after medication and radiation treatment.
Receives: Drug: Durvalumab; Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Standard of Care Therapy

What is being measured

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

  1. Maximum Tolerated Dose and Dose Limiting Toxicities

    The Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLT) will be discovered by using the 3+3 study design.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

Secondary outcomes (7)

  1. Pathologic Response

    Tumor response to neoadjuvant therapy (durvalumab + SBRT) will be assessed by pathology review of the surgical specimen. Response will be labeled as complete pathologic remission, microscopic residual tumor (only scattered foci of residual tumor cells) or macroscopic residual tumor.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  2. Clinical Response

    Overall survival (OS), along with locoregional control and distant control will be determined from the time of enrollment to date of death due to any cause. OS will be evaluated by Kaplan-Meier estimate.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  3. Evaluate Biomarkers: Gene Expression

    Analysis of gene expression of RNA levels and entire genome sequences using the 10X Genomics single-cell RNA-sequencing platform.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  4. Evaluate Biomarkers: Phenotypic Analysis

    Phenotypic analysis of T cells and assessment of intracellular and circulating cytokines using multiplex mass flow cytometry to analyze phenotypic changes, functional response of cytokine production, and activation status of tumor infiltrating lymphocytes (TILs), circulating T cells (especially CD8 and PD-1 expression), and peripheral blood mononuclear cells (PBMCs).

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  5. Evaluate Biomarkers: Immune Cell Infiltration

    Examination of intratumoral immune cell infiltration using the Perkin Elmer Vectra 3 and tissue microarrays.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  6. Toxicity Profile

    Grading of adverse effects (AEs) will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  7. Short Term Quality of Life

    Short- and long-term quality of life will be obtained using FACT H\&N v4 and will be assessed at baseline, with each cycle, post-SBRT, post-surgically, and throughout adjuvant therapy on a standard schedule.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

Timeline

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

  1. First posted17 Aug 2018
  2. Study start12 Nov 2018
  3. Primary completion9 Nov 2021
  4. Study completion2 May 2023

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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03635164
Sponsor's protocol ID
18-0606.cc
Status last verified
Jun 2025
First submitted
16 Jul 2018
Last updated
27 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Darragh LB, Knitz MM, Hu J, Clambey ET, Backus J, Dumit A, Samedi V, Bubak A, Greene C, Waxweiler T, Mehrotra S, Bhatia S, Gadwa J, Bickett T, Piper M, Fakhoury K, Liu A, Petit J, Bowles D, Thaker A, Atiyeh K, Goddard J, Hoyer R, Van Bokhoven A, Jordan K, Jimeno A, D'Alessandro A, Raben D, McDermott JD, Karam SD. A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC. Nat Cancer. 2022 Nov;3(11):1300-1317. doi: 10.1038/s43018-022-00450-6. Epub 2022 Nov 25.

    PubMed 36434392

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Durvalumab and Stereotactic Body Radiation Therapy (SBRT) in people with Squamous Cell Carcinoma of the Head and Neck, run by University of Colorado, Denver at 3 sites 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 24 inclusion and 35 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: finished, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum Tolerated Dose and Dose Limiting Toxicities (time frame: Study start date to study end date, or death, whichever comes first, up to 24 months). 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 NCT03635164, which also lists 1 linked publication.

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 27 Jun 2025.

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