Trial Title:
Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy for the Treatment of Patients With Locally Recurrent, Refractory or Oligometastatic Head and Neck Squamous Cell Carcinoma
NCT ID:
NCT06211335
Condition:
Locally Recurrent Head and Neck Squamous Cell Carcinoma
Metastatic Head and Neck Squamous Cell Carcinoma
Refractory Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Recurrence
Pembrolizumab
Losartan
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Losartan
Description:
Given PO
Arm group label:
Treatment (losartan, SBRT, pembrolizumab)
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (losartan, SBRT, pembrolizumab)
Other name:
BCD-201
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
SCH 900475
Intervention type:
Radiation
Intervention name:
Stereotactic Body Radiation Therapy
Description:
Undergo SBRT
Arm group label:
Treatment (losartan, SBRT, pembrolizumab)
Other name:
SABR
Other name:
SBRT
Other name:
Stereotactic Ablative Body Radiation Therapy
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.
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California Davis Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shyam S.D. Rao, MD, PhD
Phone:
916-734-5810
Email:
sdrao@ucdavis.edu
Investigator:
Last name:
Shyam S. Rao, MD, PhD
Email:
Principal Investigator
Start date:
December 7, 2023
Completion date:
June 2027
Lead sponsor:
Agency:
Shyam S.D. Rao
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
University of California, Davis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06211335
