Study Stopped
Unable to enroll enough patients to complete targeted enrollment in a reasonable time.
Focused Ultrasound Ablation and PD-1 Antibody Blockade in Advanced Solid Tumors
AM-003
Pilot Evaluation of Focused Ultrasound Ablation and Focused Ultrasound Ablation Plus PD-1 Antibody Blockade in Advanced Solid Tumors
1 other identifier
interventional
5
1 country
1
Brief Summary
This study evaluates whether it is safe to Focused Ultrasound Ablation (FUSA) treatments with and without PD-1 blockade and with and without intratumoral poly-ICLC. A device called the Echopulse will be used for the FUSA therapy. Patients will be assigned to 1 of 2 cohorts depending on their disease and treatment status. In Cohort 1, patients will receive FUSA therapy while receiving PD-1 blockade therapy as part of standard clinical care treatment. In Cohort 2, patients who discontinue or are ineligible for PD-1 blockade therapy will undergo FUSA without concurrent systemic therapy, with the goal of utilizing the FUSA to boost the innate immune response. The optional secondary regimen will combine FUSA (+/- PD-1 blockade) with intratumoral poly-ICLC.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2019
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 3, 2019
CompletedFirst Posted
Study publicly available on registry
October 4, 2019
CompletedStudy Start
First participant enrolled
November 21, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 15, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 15, 2023
CompletedJuly 14, 2025
August 1, 2023
3.7 years
October 3, 2019
July 10, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To assess the safety and toxicity of FUSA administered alone or in combination with PD-1 antibody blockade.
Incidence and severity of adverse events and incidence of dose-limiting toxicities (DLTs).
30 days after the last study intervention
To estimate the proportion of patients with increased CD8+ T cell infiltration of spot FUSA-treated metastasis.
Proportion of participants achieving at least a 2-fold increase in CD8+ T cell infiltration per mm2.
Day 43 (cohort 1) or Day 36 (cohort 2)
Secondary Outcomes (1)
To estimate the proportion of patients with increased CD8+ T cell infiltration, after spot FUSA, in untreated metastasis, when available.
Day 43 (cohort 1) or Day 36 (cohort 2)
Study Arms (4)
Cohort 1, primary regimen (Regimen 1a)
EXPERIMENTALFUSA therapy and standard of care PD-1 blockade. FUSA therapy will be administered on day 8.
Cohort 1, secondary regimen (Regimen 2a)
EXPERIMENTALFUSA therapy, standard of care PD-1 blockade, and intratumoral poly-ICLC will be administered on day 8.
Cohort 2, primary regimen (Regimen 1b)
EXPERIMENTALFUSA therapy will be administered on day 1.
Cohort 2, secondary regimen (Regimen 2b)
EXPERIMENTALFUSA therapy and intratumoral poly-ICLC will be administered on day 1.
Interventions
The Echopulse device delivers focused ultrasound ablation (FUSA) therapy. FUSA is a technology that delivers continuous high-intensity focused ultrasound to ablate tissue.
Poly-ICLC is a TLR3 agonist.
PD-1 therapy FDA approved for use on a 3-week schedule will be used per standard of care.
Eligibility Criteria
You may qualify if:
- Age ≥18 years.
- Advanced solid tumor with measurable disease.
- Subject must have failed or have contraindication to standard therapies.
- For Cohort 1, primary regimen (Regimen 1a): Patients with advanced solid malignancy for which PD1 or PDL1 antibody monotherapy administered on a 3-week schedule is FDA-approved for treatment, who have one or more tumor deposits that are accessible to focused ultrasound treatment, and who are eligible to receive (or to continue to receive) PD1 or PDL1 blockade therapy. Uveal melanoma patients are not eligible for Regimen 1a.
- Note: Participants eligible for this regimen may receive the primary protocol therapy (Regimen 1a) concurrent with PD1/PDL1 antibody therapy if:
- Progressive Disease: subjects with progressive disease following PD1/PDL1 antibody therapy are eligible for this cohort if it is clinically appropriate for them to continue on systemic PD1/PDL1 antibody per the treating clinician even if they did not begin treatment on this trial. Examples may include a patient with a small new lesion but stable disease in other sites, or very slight tumor growth in multiple sites, in a patient without other approved therapy options. Participants who progress following PD1/PDL1 antibody therapy may undergo interval resection of enlarging lesions and still be included in this cohort as long as they have persistent unresectable disease that is accessible to FUSA treatment.
- Response with persistent disease: subjects who have a clinical response (SD or PR) and have residual lesion(s) accessible to FUSA treatment. Participants with PR are only eligible if it is clinically appropriate for them to continue on PD1/PDL1 therapy per the judgement of the treating clinician.
- Stable disease: The majority of clinical responses to PD1/PDL1 blockade occur within 12 weeks but may occur much later. Routine clinical practice commonly includes continuation of PD1 antibody therapy for 1-2 years for patients with stable disease on that therapy. Thus, patients with SD after 12 weeks of PD1/PDL1 therapy per RECIST criteria may be eligible for Regimen 1a if their disease has remained stable on therapy and if their treating provider recommends continuation of PD1/PDL1 therapy even if they were not treated on this trial.
- For Cohort 1, secondary regimen (Regimen 2a): For those patients treated with primary regimen 1a, select participants may be enrolled in a secondary regimen. This would include participants in the following scenarios:
- Stable disease.
- Response in lesion treated in regimen 1, but persistent disease or progression in a separate lesion.
- Initial partial response but still persistent disease at the treated lesion.
- Patients enrolling to Regimen 2a must have a target lesion amenable to intratumoral injection with polyICLC per the treating clinician's discretion. The lesion(s) to be FUSA treated in regimen 2 do not need to include the lesion targeted in regimen 1. The patient must remain eligible for PD1/PDL1 Ab therapy.
- For Cohort 2, primary regimen (Regimen 1b): The following patient subsets would be eligible for the Cohort 2 primary regimen, as long as they have failed (progressed or not tolerated) or are not eligible for all effective available approved therapies known to confer clinical benefit:
- Patients with advanced solid malignancy for which PD1 or PDL1 blockade is not FDA-approved.
- +32 more criteria
You may not qualify if:
- A subject will be excluded from participating in the trial if the subject:
- Has received the following medications or treatments at any time within 3 weeks of study day 1:
- Immune therapies including:
- interferon (e.g. Intron-A®),
- checkpoint blockade therapies other than anti-PD-1/PD-L1 antibodies,
- antibodies to costimulatory molecules (e.g. CD27, CD137),
- small molecule immune therapies (e.g. IDO1 inhibitor)
- Cytotoxic chemotherapy for cancer
- Has received the following medications or treatments at any time within 4 weeks of study day 1:
- Radiation therapy (Note: Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week prior to registration)
- Allergy desensitization injections
- High doses of systemic corticosteroids, with the following qualifications and exceptions:
- Daily doses of 10 mg or less prednisone (or equivalent) per day administered parenterally or orally are allowed in patients with normal adrenal and pituitary function.
- In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed.
- Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent)
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Craig L Slingluff, Jrlead
- Theraclioncollaborator
Study Sites (1)
University of Virginia
Charlottesville, Virginia, 22908, United States
Related Publications (1)
Sheybani ND, Witter AR, Thim EA, Yagita H, Bullock TNJ, Price RJ. Combination of thermally ablative focused ultrasound with gemcitabine controls breast cancer via adaptive immunity. J Immunother Cancer. 2020 Aug;8(2):e001008. doi: 10.1136/jitc-2020-001008.
PMID: 32819975DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lynn Dengel, MD, MSc
University of Virginia
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor of Surgery; Director, Human Immune Therapy Center
Study Record Dates
First Submitted
October 3, 2019
First Posted
October 4, 2019
Study Start
November 21, 2019
Primary Completion
August 15, 2023
Study Completion
August 15, 2023
Last Updated
July 14, 2025
Record last verified: 2023-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Data may be available after the main findings from the final research data set have been accepted for publication.
- Access Criteria
- Requests for data access will be accepted only with an accompanying signed Data Access Agreement.
De-identified individual participant data that underlie the results of this study may be shared.