Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy for the Treatment of Patients With Locally Recurrent, Refractory or Oligometastatic Head and Neck Squamous Cell Carcinoma

NCT06211335 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UCDCC311NCI-2023-10476P30CA093373
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This phase Ib trial tests the safety, side effects and how well losartan, pembrolizumab and stereotactic body radiation therapy (SBRT) for the treatment of patients with head and neck squamous cell carcinoma that has come back to nearby tissue or lymph node after a period of improvement (locally recurrent), that has not responded to previous treatment (refractory) or that has spread from where it first started to multiple other placed in the body (oligometastatic). Losartan is a drug used to treat high blood pressure that may enhance the effects of other cancer treatments such as immunotherapy and radiation. Immunotherapy with pembrolizumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving losartan, pembrolizumab and SBRT may work better in treating patients with locally recurrent, refractory or oligometastatic head and neck squamous cell carcinoma.

Conditions

Metastatic Head and Neck Squamous Cell Carcinoma; Locally Recurrent Head and Neck Squamous Cell Carcinoma; Refractory Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment related adverse events

  Classified by severity and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and summarized using descriptive statistics in participants treated with dosage of the agent selected in the safety run.

  Up to 2 years

Secondary Outcomes (4)

• Objective response rate

  Up to 2 years

• Progression free survival

  From start of stereotactic body radiation therapy (SBRT) to local or distant progression or death due to any cause, up to 2 years

• Duration of response

  From CR or PR until progressive disease, death or last tumor assessment using RECIST 1.1, up to 2 years

• Overall survival

  From the start of SBRT to death from any cause, up to 2 years

Study Arms (1)

Treatment (losartan, SBRT, pembrolizumab)

EXPERIMENTAL

Patients receive losartan PO QD. One week later patients receive SBRT 2-3 times per week for approximately 2 weeks. Within 1 week of completing SBRT, patients receive pembrolizumab IV and repeat every 3 weeks. Treatment continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET, tumor biopsy, and blood sample collection throughout the study.

Drug: Losartan; Biological: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Losartan DRUG

Given PO

Treatment (losartan, SBRT, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, Keytruda, Lambrolizumab, MK-3475, Pembrolizumab Biosimilar BCD-201, SCH 900475

Treatment (losartan, SBRT, pembrolizumab)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Treatment (losartan, SBRT, pembrolizumab)

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 locoregionally recurrent, refractory, or oligometastatic (at most 4 lesions) squamous cell carcinoma of the head and neck not amenable to curative resection
• p16 status known for base of tongue, soft palate, and tonsil cancers
• Tumor amenable to sequential biopsies, and patients willing to undergo sequential tumor biopsies so long as the treating investigator considers them to be clinically safe
• Prior radiotherapy to the head and neck is allowed. Disease should be limited to up to 4 sites of active disease in the head and neck and/or distant metastatic sites if deemed safely treatable by physician, or adjacent sites treatable in single contiguous target volume with a recommended maximum total tumor dimension (GTV) of \< 7.5 cm. However, larger volumes may be allowed after discussion with primary investigator (PI) and careful review of radiation dose constraints
• Prior systemic therapy is allowed. Patients with locoregional relapses where radiation alone would be indicated are allowed to enroll without prior systemic therapy
• Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with a target on a computed tomography (CT) scan or magnetic resonance imaging (MRI) available for review
• Combined positive score (CPS) \> 1%
• Age ≥ 18 years at time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Leukocytes ≥ 3 × 10\^9/L
• Absolute neutrophil count ≥ 1.5 × 10\^9/L
• Platelets ≥ 100 × 10\^9/L
• Hemoglobin (Hgb) ≥ 9 g/dL, transfusions may be used to raise Hgb to ≥ 9 g/dL (no washout required)
• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
• Aspartate transaminase (AST) / alanine transaminase (ALT) ≤ 2.5 × institutional ULN

You may not qualify if:

• Nasopharyngeal carcinoma, salivary gland carcinoma or primary skin squamous cell carcinoma (SCC)
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody
• Chemotherapy or other anti-cancer therapy within 3 weeks prior to study day 1
• Hypersensitivity to losartan or any component of the formulation
• Radiation therapy within 6 months prior to study day 1
• Patients with disease surrounding \> 50% of the carotid
• Participant who has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 1 from an adverse event (AE) due to previous cancer therapeutics (i.e., chemotherapy, radiation therapy, biologic therapy, and/or experimental therapy) with the exception of alopecia
• Major surgery as assessed by the investigator (with the exception of diagnostic biopsy) within ≤ 28 days prior to study day 1 (patients must have completely recovered from any previous surgery prior to study day 1)
• Clinically significant bleeding ≤ 4 weeks prior to study day 1
• Requirement for parenteral antibiotics, or any active infection requiring parenteral antibiotic therapy within 4 weeks prior to study day 1
• Clinically significant or uncontrolled diabetes mellitus (hemoglobin A1C ≤ 8.5%). Patients with diabetes mellitus treated with aliskiren ≤ 7 days prior to study day 1 are excluded
• Active autoimmune disorders that have required systemic treatment with disease modifying agents, corticosteroids, or immunosuppressive drugs in the past 2 years are excluded. Patients with autoimmune disorder or well-managed or inactive autoimmune disorders, such as Hashimoto's thyroiditis, may be allowed at the discretion of the PI
• Current use of systemic corticosteroids equivalent to \>10 mg of prednisone per day
• Current use of angiotensin receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors for management of hypertension
• Clinically significant cardiovascular, pulmonary, endocrine, neurologic, gastrointestinal or genitourinary disease unrelated to underlying solid tumor that in the judgment of the investigator should preclude treatment with losartan

Sponsors & Collaborators

• University of California, Davis: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

University of Colorado Denver | Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Losartan; pembrolizumab; 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)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Shyam S.D. Rao, MD, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Office of Clinical Research

CONTACT

916-382-6970; OCRReferral@health.ucdavis.edu

Study Design

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

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 18, 2024
• Study Start: December 7, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (2)