Radiotherapy in Combination With Atezolizumab Prior to Surgical Resection for HPV Unrelated HNSCC

Completed · Phase 1

Conditions studied: Squamous Cell Carcinoma of Head and Neck

In brief

To determine the outcomes of patients with specific head and neck cancer after undergoing radiation therapy with atezolizumab followed by surgery then radiation with or without chemotherapy according to national guidelines.

Key facts

Study ID

NCT05053737

Run by

University of Colorado, Denver

People needed

11

Starts

2021-11-02

Expected to finish

2024-06-21

Last updated by the study team

2025-02-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Provision to sign and date the consent form
• Stated willingness to comply with all study procedures and be available for the duration of the study
• Histologically or cytologically confirmed: stage II-IVB oral cavity, stage III-IVB larynx, stage III-IVB hypopharynx, stage III-IVB sinonasal, 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
• Age ≥ 18 years at time of study entry
• ECOG performance status ≤ 1
• Body weight >30 kg
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥ 1500 per mm3) without granulocyte colony-stimulating factor support.
• Lymphocyte count ≥0.5 × 109/L (500/μL)
• Platelet count ≥100 x 109/L (≥100,000 per mm3) without transfusion
• 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)/ ALP ≤2.5 x institutional upper limit of normal
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 × ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• 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)
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. See section 6.12 for additional details and contraception requirements for patients on study. 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)

You may not qualify if…

• 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 PD-1 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)
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• 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
• Current or prior use of immunosuppressive medication within 14 days before the first dose of atezolizumab, 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
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled 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
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• 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
• Active or previously treated prostate cancer without distant metastasis
• Active or previously treated thyroid cancer without distant metastasis

Where it is running

• Colorado Research Center — Aurora, Colorado, United States
• Memorial Health Central — Colorado Springs, Colorado, United States
• Memorial Hospital North — Colorado Springs, Colorado, United States
• Highlands Ranch Hospital — Highlands Ranch, Colorado, United States

Full record on ClinicalTrials.gov

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