- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06211335
Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy for the Treatment of Patients With Locally Recurrent, Refractory or Oligometastatic Head and Neck Squamous Cell Carcinoma
Phase Ib Study of Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy (SBRT) in Patients With Locoregionally Recurrent, Refractory, or Oligometastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:I. Determine the safety and toxicity of losartan in combination with SBRT and subsequently pembrolizumab in patients with locally recurrent, refractory, or oligometastatic head and neck squamous cell carcinoma (HNSCC).
SECONDARY OBJECTIVES:I. Evaluate objective tumor response.II. Evaluate progression free survival (PFS). III. Evaluate duration of response.IV. Evaluate overall survival (OS).
OUTLINE:Patients receive losartan orally (PO) once daily (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 intravenously (IV) and repeat every 3 weeks. Treatment continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET), tumor biopsy, and blood sample collection throughout the study.After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 1 year.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
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Sacramento, California, United States, 95817
- Recruiting
- University of California Davis Comprehensive Cancer Center
-
Contact:
- Shyam S.D. Rao, MD, PhD
- Phone Number: 916-734-5810
- Email: sdrao@ucdavis.edu
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Principal Investigator:
- Shyam S. Rao, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- Creatinine within normal institutional limits OR creatinine clearance ≥ 30 mL/min/1.73 m^2 for patients with creatinine above institutional ULN
- The effects of losartan on the developing human fetus are unknown. For this reason, individuals of childbearing potential and male participants with partners of childbearing potential, must agree to use methods of contraception for the duration of study participation (including dosing interruptions) and for up to 3 months after last study treatment; or be surgically sterilized
- Ability to understand and willingness to sign and date the informed consent form
- Stated ability and willingness to adhere to the study visit schedule and protocol requirements
Exclusion Criteria:
- 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
- Any other active malignancy except for low-risk prostate cancer previously treated or under active surveillance, uncomplicated and cured basal cell carcinoma, or squamous cell carcinoma of the skin within 5 years of study entry
- Known history of positive hepatitis C (HCV) antibody, hepatitis B (HBV) surface antigen (HbsAg and HBV core Ab positive), or human immunodeficiency virus (HIV) antibody results. Patients with positive antibody tests are eligible with negative viral loads
- Administration of live, attenuated vaccine ≤ 28 days prior to study day 1. Administration of inactivated flu vaccines is allowed
- Any prior treatment with losartan or other specific TGF-β-directed therapy
- Treatment with another investigational drug or device, or approved therapy for investigational use ≤ 28 days prior to study day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to study day 1, whichever may be longer
- Pregnant or breast feeding
- Any condition that in the opinion of the investigator would interfere with the participant's safety, compliance while on trial, or understanding or rendering of informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (losartan, SBRT, pembrolizumab)
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.
|
Given IV
Other Names:
Undergo SBRT
Other Names:
Given PO
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment related adverse events
Time Frame: Up to 2 years
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate
Time Frame: Up to 2 years
|
Defined as stable disease, complete response (CR) or partial response (PR) on imaging assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Will be summarized using Kaplan-Meier curves and 95% confidence interval (CI).
Median and range will be reported.
|
Up to 2 years
|
Progression free survival
Time Frame: From start of stereotactic body radiation therapy (SBRT) to local or distant progression or death due to any cause, up to 2 years
|
According to RECIST 1.1.
Will be summarized using Kaplan-Meier curves and 95% CI.
|
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
Time Frame: From CR or PR until progressive disease, death or last tumor assessment using RECIST 1.1, up to 2 years
|
Median and range will be reported.
|
From CR or PR until progressive disease, death or last tumor assessment using RECIST 1.1, up to 2 years
|
Overall survival
Time Frame: From the start of SBRT to death from any cause, up to 2 years
|
Will be summarized using Kaplan-Meier curves and 95% CI.
|
From the start of SBRT to death from any cause, up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Shyam S.D. Rao, MD, PhD, University of California, Davis
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Head and Neck Neoplasms
- Neoplasms, Squamous Cell
- Carcinoma
- Recurrence
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Pembrolizumab
- Losartan
Other Study ID Numbers
- UCDCC311 (Other Identifier: University of California Davis Comprehensive Cancer Center)
- P30CA093373 (U.S. NIH Grant/Contract)
- NCI-2023-10476 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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