Pembrolizumab Plus Ultrasound-Induced Microbubble Cavitation in Head and Neck Cancer

NCT07501650 | Recruiting Phase 1 FDA Drug FDA Device

• 2 other identifiers: iRISID-2025-0984JT 45752
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a feasibility trial studying anti-PD-1 therapy (Pembrolizumab) among patients with R/M HNSCC, delivered with ultrasound-induced microbubble cavitation, with the goal of optimizing delivery of Pembrolizumab and tumor response to Pembrolizumab. Patients will undergo 3 infusions of Pembrolizumab plus Definity 3 weeks apart. Following each infusion, ultrasound will be directed at the primary tumor site to induce microbubble cavitation, with the goal of tumor sonoporation. The primary endpoints will be feasibility, measured based on successful recruitment of 6 participants within 1 year of initiating recruitment, with successful completion of trial procedures among at least 80 percent of patients. Secondary endpoints will include proportion of serious adverse events, clinical/radiographic response, overall survival, and progression-free survival.

Conditions

Head and Neck Cancer; Head and Neck Small Cell Carcinoma; Metastatic Head and Neck Cancer; Recurrent Head and Neck Cancer

Keywords

Recurrent; Pembrolizumab; Pembro; Microbubble; Cavitation

Outcome Measures

Primary Outcomes (1)

• Number of Participants who complete all planned treatment cycles

  The number of participants who completed trial procedures among at least 80 percent of patients, among patients with recurrent or metastatic head and neck squamous cell carcinoma.

  Up to 9 weeks

Secondary Outcomes (5)

• Number of Treatment-Related Adverse Events (TRAEs)

  Up to 6 months post-treatment

• Objective Response Rate using RECIST v1.1

  Up to 3 months after last treatment

• Overall Survival

  90 days after last dose

• Disease-Free Survival

  90 days after last dose

• Progression-Free Survival

  90 days after last dose

Study Arms (1)

Arm 1: Pembro + Ultrasound-Induced Microbubble Cavitation

EXPERIMENTAL

Treatment will be administered on an outpatient basis. 200 mg Pembrolizumab + 3 mL Definity infusions will be administered by nurses at Thomas Jefferson University every 3 weeks for up to 3 cycles. The first cycle will take 60 minutes, while the subsequent infusions should take half an hour to complete.

Drug: Pembrolizumab; Drug: Definity; Device: Ultrasound-Induced Microbubble Cavitation

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered intravenously at a dose of 200 mg every 3 weeks for up to 3 cycles

Also known as: Keytruda

Arm 1: Pembro + Ultrasound-Induced Microbubble Cavitation

Definity DRUG

Definity will be administered intravenously during each treatment cycle to facilitate ultrasound-induced microbubble cavitation.

Also known as: Definity RT, perflutren lipid microsphere

Arm 1: Pembro + Ultrasound-Induced Microbubble Cavitation

Ultrasound-Induced Microbubble Cavitation DEVICE

Therapeutic Ultrasound will be applied to the tumor site during and following the Definity infusion to induce microbubble cavitation using modified ultrasound parameters.

Also known as: Therapeutic Ultrasound

Arm 1: Pembro + Ultrasound-Induced Microbubble Cavitation

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed, HPV-negative, R/M HNSCC per American Joint Committee on Cancer (AJCC) 8th Edition Staging Criteria, with CPS score \> 1
• The target lesion is ultrasound-accessible, biopsy-accessible, and measurable in at least one dimension, based on RECISTv1.1 criteria.
• Male or female, aged ≥18 years of age
• ECOG Performance status 0-2.
• Must have a life expectancy of at least 6 months as judged by the treating physician.
• Adequate organ function:
• Absolute neutrophil count 1500/μl or more;
• Platelets 100,000/μl or more,
• Hemoglobin 8 g/dl or more;
• Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \<3 mg/dl);
• AST and ALT less than or equal to 2.5x the upper limit of normal
• Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG), which must also be confirmed as negative within 28 days of the start of study drugs.
• Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 90 days after the last dose of study drugs. "Women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, tubal ligation, or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
• Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year. Men who are receiving the study medications will be instructed to adhere to contraception for 90 days after the last dose of study drugs. Men who are azoospermic do not require contraception.
• Informed Consent: All subjects must be able to comprehend and sign a written informed consent document.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Patients with HPV-positive or p16-positive SCC
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or antiCTLA-4 antibody
• Any history of allergy to the study drug components, including to polyethyleneglycol or medications containing polyethylene glycol.
• Patients with the following cardiac conditions or history:
• Patients with a known history of anatomic right-to-left, bi-directional, or transient right-to-left cardiac shunts
• Patients with NYHA class III or greater heart failure, unstable anginal syndrome, or experiencing active chest pain.
• Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 200 mmHg or diastolic blood pressure ≥ 110 mmHg) or arterial hypotension (defined as systolic blood pressure ≤ 90 mmHg)
• Patients who have experienced a STEMI or NSTEMI within the last 6 months
• QTc \>500 as determined by Fridericia correction
• Patients with a history of ventricular arrhythmia that has not been corrected by placement of a PPM or ICD
• Any concurrent malignancies: exceptions include- cutaneous basal cell carcinoma, chronic lymphocytic leukemia, melanoma in situ, squamous cell carcinoma of the skin of a secondary location, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 2 years post-diagnosis.
• Any subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 28 days of study drug administration., or a prior history of allogenic organ transplantation.
• Any active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Patients must not be receiving any other investigational agents; must not have participated in a study of an investigational agent or be using an investigational device within 4 weeks of the first dose of Pembrolizumab plus Definity.

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Lantheus Medical Imaging: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Recurrence

Interventions

pembrolizumab; perflutren; Ultrasonic Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diathermy; Hyperthermia, Induced; Therapeutics

Study Officials

• Joseph M Curry, MD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph M Curry, MD

CONTACT

215-955-6760; Joseph.Curry@jefferson.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: March 24, 2026
• First Posted: March 30, 2026
• Study Start: March 18, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (1)