Atezolizumab Before Surgery for the Treatment of Regionally Metastatic Head and Neck Squamous Cell Cancer With an Unknown or Historic Primary Site

NCT05110781 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: UCDCC#295NCI-2021-10734P30CA093373
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests whether atezolizumab works to shrink tumors before surgery in patients with head and neck squamous cell cancer with an unknown or historic primary site that has spread to other places in the lymph nodes (regionally metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab before surgery may reduce the size of the tumor.

Conditions

Locally Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck; Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck; Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR)

  pCR is defined as having no residual invasive squamous cell carcinoma within the primary tumor and all resected lymph nodes as assessed by the pathologist at the time of primary resection. The rate of pCR is defined as the proportion of patients demonstrating pCR.

  At time of surgery (up to 10 weeks from time of enrollment)

Secondary Outcomes (6)

• Major Pathologic Response (mPR)

  At time of surgery (up to 10 weeks from time of enrollment)

• Number of Participants With Recurrence or Disease Progression

  From randomization to the first day of radiographic evidence of recurrence or disease progression, clinical evidence of recurrence or disease progression, or death due to any cause, whichever occurs first, assessed at 2 years

• Standardized Uptake Value (SUV) of Primary Lesion Assessed at Baseline and 3 Months After Completion of Treatment

  At baseline and 3 months after completion of treatment

• Number of Participants With Overall Response

  Up to 3 years

• Plasma Exosome Levels

  Up to 3 years

Study Arms (1)

Treatment (atezolizumab, surgery, radiation therapy)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery. Beginning 6 weeks after surgery, patients with residual disease undergo standard of care radiation therapy and receive atezolizumab IV over 30-60 minutes on day 1. Treatment with atezolizumab repeats every 21 days for up to 15 cycles in the absence of disease progression and unacceptable toxicity.

Biological: Atezolizumab; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (atezolizumab, surgery, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (atezolizumab, surgery, radiation therapy)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (atezolizumab, surgery, radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Participants with biopsy proven, surgically resectable head and neck cutaneous squamous cell carcinoma regionally metastatic to lymph nodes in the head and/or neck with a historical or unknown (but not concurrent) primary site
• Patients must be \>= 18 years
• Patients with resectable regionally metastatic HNCSCC from an unknown or historical primary and no evidence of distant metastatic disease
• Full decision-making capacity and consent provided and documented
• Radiographically measurable disease per immune Response Evaluation Criteria in Solid Tumors (iRECIST)
• Surgically resectable disease per standard of care (SoC)
• For Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods as defined below: \* Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final dose of atezolizumab \* A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements \* Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices \* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
• Men: abstinent or using effective contraception method
• Tumor tissue sample adequate for PD-L1 and biomarker studies
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Availability of a representative tumor specimen for exploratory biomarker research
• Life expectancy \>= 2 years
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1500/uL) without granulocyte colony-stimulating factor support (within 14 days prior to initiation of study treatment)
• Lymphocyte count \>= 0.5 x 10\^9/L (500/uL) (within 14 days prior to initiation of study treatment)
• Platelet count \>= 50 x 10\^9/L (50,000/uL) without transfusion (within 14 days prior to initiation of study treatment)

You may not qualify if:

• Distant metastatic disease
• Unresectable disease: As defined by: common or internal carotid artery encasement or involvement of the skull base involvement or pre-vertebral fascia
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) \* Patients with indwelling catheters (e.g., PleurX) are allowed
• Uncontrolled (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN) or symptomatic hypercalcemia
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions: \* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study \* Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study \* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: \*\* Rash must cover \< 10% of body surface area \*\* Disease is well controlled at baseline and requires only low-potency topical corticosteroids \*\* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months \* Any history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Known active tuberculosis
• 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
• 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
• History of malignancy within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival \[OS\] rate \> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer
• 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. Severe infection is defined as that requiring inpatient treatment of hospitalization
• 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
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 6 months after the final dose of atezolizumab

Sponsors & Collaborators

• Arnaud Bewley, MD: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Interventions

atezolizumab; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Limitations and Caveats

One participant was enrolled in study prior to termination. Enrollment in the clinical trial did not reach the target number of participants needed to achieve target power and was insufficient to produce statistically reliable results.

Results Point of Contact

• Title: Principal Investigator
• Organization: University of California, Davis

abewley@UCDAVIS.EDU

916-734-2790

Study Officials

• Arnaud Bewley

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 13, 2021
• First Posted: November 8, 2021
• Study Start: December 7, 2021
• Primary Completion: May 2, 2022
• Study Completion: April 18, 2023
• Last Updated: September 5, 2023
• Results First Posted: September 5, 2023

Record last verified: 2023-08

Locations

US (1)