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

NCT05053737 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 21-2642.cc
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (2)

• Phase I lead in: Primary Outcome is Safety determined by Adverse Events

  Phase I lead in: the primary endpoint will be the binary outcome of whether or not a patient experiences the occurrence of a dose-limiting toxicity (DLT). Adverse events will be reviewed for safety assessments.

  24 months

• Phase II: Primary Endpoint is Efficacy as measured by the rate of MPR

  Phase II: the primary endpoint will be efficacy as measured by the rate of MPR (≤10% residual tumor) or pathologic complete response (pCR, no residual tumor). Response will be assessed by pathology review and will be labeled as pathologic tumor response 0 (pTR-0, \<10% of sample characterized by tumor necrosis, keratinous debris, and/or giant cells/histiocytes), pTR-1 (10-49%), pTR-2 (50-89%), MPR (90-99%, also referred to pTR-3), or complete pathologic response (pCR, 100%, also referred to as pTR-4).

  24 months

Secondary Outcomes (1)

• Survival

  24 months

Other Outcomes (2)

• Translational Endpoints

  24 months

• Secondary Translational Endpoint

  24 months

Study Arms (2)

Phase 1 Lead-in SBRT with Neoadjuvant Atezolizumab

EXPERIMENTAL

Initially 3 patients will be enrolled to receive one dose of neoadjuvant atezolizumab with 3 fractions of 8 Gy SBRT (dose level 2, i.e. starting dose). If there are \< = 1 DLT related to the neoadjuvant therapy, another 3 patients will be enrolled at the same SBRT dose with only one cycle of neoadjuvant atezolizumab. And if there are \<= 1 DLT out of the 6 patients, then determine MTD at this dose level.

Drug: Atezolizumab; Radiation: Stereotactic Body Radiation Therapy

SBRT with Neoadjuvant Atezolizumab

EXPERIMENTAL

After the MTD is determined, additional patients will be enrolled at this dose level to ensure 14 patients evaluable for the efficacy endpoints (MPR) at the planned interim analysis. The 6 patients treated at the MTD in phase I will be included if evaluable for MPR, so that additional 8 patients will be enrolled in this stage.

Drug: Atezolizumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Atezolizumab DRUG

One cycle of Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg. Atezolizumab should be administered within 7 days after initiation of of the first dose of SBRT.

Also known as: MPDL3280A, RG7446, Tecentriq

Phase 1 Lead-in SBRT with Neoadjuvant Atezolizumab; SBRT with Neoadjuvant Atezolizumab

Stereotactic Body Radiation Therapy RADIATION

SBRT will be given 3 times on non-consecutive days over the course of 5 to 7 days. Radiation will target sites of gross disease only to minimized exposure to normal tissue.

Also known as: SBRT

Phase 1 Lead-in SBRT with Neoadjuvant Atezolizumab; SBRT with Neoadjuvant Atezolizumab

Eligibility Criteria

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

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

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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Genentech, Inc.: collaborator

Study Sites (4)

Colorado Research Center

Aurora, Colorado, 80045, United States

Location

Memorial Health Central

Colorado Springs, Colorado, 80909, United States

Location

Memorial Hospital North

Colorado Springs, Colorado, 80920, United States

Location

Highlands Ranch Hospital

Highlands Ranch, Colorado, 80129, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

atezolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Sana Karam, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: HPV unrelated head and neck cancer. Neoadjuvant Atezolizumab w/ SBRT followed by surgery then risk adjusted adjuvant therapy per NCCN guidelines (adjuvant RT or CRT)

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: September 22, 2021
• Study Start: November 2, 2021
• Primary Completion: November 24, 2023
• Study Completion: June 21, 2024
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)