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MelanomaPhase 1AM-003NCT04116320

Focused Ultrasound Ablation and PD-1 Antibody Blockade in Advanced Solid Tumors

A Phase 1 study testing Echopulse and Poly ICLC in people with Melanoma and Breast Cancer, run by Craig L Slingluff, Jr at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma, Breast Cancer, Merkel Cell Carcinoma
What is being tested?
Echopulse and Poly ICLC
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
21 Nov 2019to 15 Aug 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Initial response followed by progression at treated lesion or separate site, after discontinuation of PD-1/PD-L1 antibody. If there is a response and then progression at the site treated in Regimen 1 and the residual tumor meets inclusion criteria, this lesion may be re-treated on the secondary regimen.
  • Participants with lesions unique from the lesion treated in regimen 1 may enroll in regimen 2 and have additional lesion(s) treated, as long as they meet all inclusion criteria requirements. Up to three lesions may be treated in the second regimen.
  • 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.
  • Patients with metastatic uveal melanoma
  • Patients with advanced solid malignancies for which PD1 or PDL1 blockade is FDA approved but who are not eligible to receive that therapy because of prior failure, toxicity, baseline autoimmune disease, or frailty.
  • Patients who previously responded to PD1/PDL1 therapy but then progressed, if there are no other systemic therapies available to them.
  • Patients who were previously undergoing PD-1 blockade therapy must not have received a dose within 4 weeks prior to FUSA treatment.
  • For Cohort 2, secondary regimen (Regimen 2b): For those patients treated with primary regimen 1a or 1b, 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.
  • Initial response followed by progression at the treated lesion after discontinuation of PD-1/PD-L1 antibody. If there is a response and then progression at the site treated in Regimen 1 and the residual tumor meets inclusion criteria, this lesion may be re-treated on the secondary regimen. For participants who progress at a site unique from the treated lesion, they may enroll in Regimen 2 and have this new lesion treated, as long as they meet all inclusion criteria requirements.
  • Participants with lesions unique from the lesion treated in regimen 1 may enroll in regimen 2 and have additional lesion(s) treated, as long as they meet all inclusion criteria requirements. Up to three lesions may be treated in the second regimen.
  • Patients enrolling to Regimen 2b must have a target lesion amenable to intratumoral injection with polyICLC per the treating clinician's discretion. The lesion to be FUSA treated in regimen 2 does not need to be the same lesion targeted in regimen 1. Crossover from primary regimen 1a is allowed if the patient is no longer eligible for continued PD1/PDL1 Ab therapy (e.g. due to autoimmune toxicity), and if there is no other effective systemic therapy option. The length between the FUSA treatments in regimen 1 and regimen 2 should be no less than 6 weeks. Patients who experienced an unanticipated device effect in the primary regimen are not eligible for the secondary regimen.
  • One or more dermal, subcutaneous or nodal metastases from an advanced solid tumor. The metastases need to be accessible for FUSA and for biopsy.
  • For FUSA:
  • The targeted lesion(s) must be visible by ultrasound imaging and meet the following criteria. Brain lesions may not be targeted for treatment.
  • Approximately 1 cm (or more) diameter of treatable tumor volume for lesions to be treated with FUSA.
  • The target treatment area needs to be contained within a region at least 5 mm from the skin surface and less than or equal to 23 mm from the skin surface.
  • The target treatment area must be at a safe distance from all critical structures, including but not limited to ribs or other bony structures, vital organs, named blood vessels or nerves.
  • The critical structures, with the exception of the skin, will not be in the pre-focal ultrasound path.
  • The anterior-posterior dimension of the treatment area by US should be no less than 9mm.
  • For Biopsies:
  • Biopsies may be completed with or without image guidance.
  • Lesions that have been selected for focused ultrasound or lesions that have been selected for biopsies as untreated controls may have been previously radiated provided:
  • The tumor site that was previously radiated has progressed.
  • A baseline biopsy of the tumor site is obtained following progression and prior to study entry.
  • ECOG performance status 0-2.
  • Subjects with brain metastases may participate if all of the following are true:
  • There has been no evident growth of any brain metastasis since the most recent treatment
  • No brain metastasis is > 2 cm in diameter at the time of registration.
  • Neurologic symptoms have returned to baseline,
  • There is no evidence of new or enlarging brain metastases,
  • Subjects are not using steroids for at least 7 days prior to registration. Regardless of dose, however, subjects who are on a steroid taper for management of brain metastases are not eligible until 7 days after completion of that steroid taper.
  • Brain metastases will not be targeted for FUSA treatment.
  • Adequate organ function
  • Ability and willingness to give informed consent.

Who cannot join

  • 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),
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  • 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)
  • Topical and nasal corticosteroids are acceptable.
  • Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
  • Interleukins (e.g. Proleukin®)
  • Any investigational therapeutic agent (participation in the UVA AM004 clinical trial is permitted)
  • Targeted therapies specific for mutated BRAF or for MEK
  • Live vaccine
  • Has a known addiction to alcohol or drugs and is actively taking those agents, or has recently (within 1 year) taken these agents or has ongoing illicit IV drug use.
  • Is HIV positive or has evidence of active Hepatitis B or C virus with some exceptions.
  • Is currently receiving nitrosoureas or has received this therapy within the preceding 6 weeks
  • Is pregnant or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test obtained within 2 weeks prior to registration. Males and females must agree, in the consent form, to use effective birth control methods during the course of treatment and following treatment in accordance with the labeling guidelines for each approved therapy.
  • Has a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.
  • Has an active infection requiring systemic therapy.
  • Has Class III or IV heart disease as classified according to the New York Heart Association.
  • Has had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy,or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded.
  • Note: The following are not exclusionary:
  • The presence of laboratory evidence of autoimmune disease (e.g. positive ANA titer) without symptoms
  • Clinical evidence of vitiligo
  • Other forms of depigmenting illness
  • Mild arthritis requiring NSAID medications
  • A history of immune-related adverse events with immune therapy, if the immune-related adverse events have resolved to grade 1 or lower.
  • History of another cancer
  • Note: the following diagnoses are exceptions and are permitted as long as they have been treated successfully and without clinical evidence of disease:
  • Any cancer that has been treated successfully, without evidence of subsequent recurrence or metastasis for over 5 years
  • Any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 2 years
  • Squamous cell cancer of the skin without known metastasis
  • Basal cell cancer of the skin without known metastasis
  • Carcinoma in situ of the breast (DCIS or LCIS)
  • Carcinoma in situ of the cervix
  • 12) Previous treatment with polyICLC within 4 weeks. If a subject was previously treated with intratumoral polyICLC and experienced a significant (grade ≥3) toxicity related to the polyICLC treatment, the tumor that was treated should not be re-treated as part of this protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Virginia

    Charlottesville, Virginia, 22908

Other trials in United States

About this study

Official title: Pilot Evaluation of Focused Ultrasound Ablation and Focused Ultrasound Ablation Plus PD-1 Antibody Blockade in Advanced Solid Tumors

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.

Being tested
Echopulse, Poly ICLC, Standard of Care PD-1 Therapy
Keywords
Echopulse, Focused Ultrasound Ablation, FUSA, Pembrolizumab, Keytruda, Atezolizumab, Tecentriq, polyICLC, poly-ICLC, Hiltonol
Medical subject headings
Melanoma, Breast Neoplasms, Carcinoma, Merkel Cell, Neoplasms, Squamous Cell, Carcinoma, Non-Small-Cell Lung, Uterine Cervical Neoplasms, Carcinoma, Transitional Cell, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EchopulseDevice

    Also called Focused Ultrasound Ablation, FUSA

    The Echopulse device delivers focused ultrasound ablation (FUSA) therapy. FUSA is a technology that delivers continuous high-intensity focused ultrasound to ablate tissue.

  • Poly ICLCDrug

    Also called Hiltonol

    Poly-ICLC is a TLR3 agonist.

  • Standard of Care PD-1 TherapyDrug

    PD-1 therapy FDA approved for use on a 3-week schedule will be used per standard of care.

Study groups in NCT04116320
Study groupRoleWhat they receive
Cohort 1, primary regimen (Regimen 1a)ExperimentalFUSA therapy and standard of care PD-1 blockade. FUSA therapy will be administered on day 8.
Receives: Device: Echopulse; Drug: Standard of Care PD-1 Therapy
Cohort 1, secondary regimen (Regimen 2a)ExperimentalFUSA therapy, standard of care PD-1 blockade, and intratumoral poly-ICLC will be administered on day 8.
Receives: Device: Echopulse; Drug: Poly ICLC; Drug: Standard of Care PD-1 Therapy
Cohort 2, primary regimen (Regimen 1b)ExperimentalFUSA therapy will be administered on day 1.
Receives: Device: Echopulse
Cohort 2, secondary regimen (Regimen 2b)ExperimentalFUSA therapy and intratumoral poly-ICLC will be administered on day 1.
Receives: Device: Echopulse; Drug: Poly ICLC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 30 days after the last study intervention

  2. 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.

    Measured: Day 43 (cohort 1) or Day 36 (cohort 2)

Secondary outcomes (1)
  1. To estimate the proportion of patients with increased CD8+ T cell infiltration, after spot FUSA, in untreated metastasis, when available.

    Proportion of participants achieving at least a 2-fold increase in CD8+ T cell infiltration per mm2

    Measured: Day 43 (cohort 1) or Day 36 (cohort 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2019
  2. Study start21 Nov 2019
  3. Primary completion15 Aug 2023
  4. Study completion15 Aug 2023

Why it stopped: Unable to enroll enough patients to complete targeted enrollment in a reasonable time.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04116320
Sponsor's protocol ID
21850
Acronym
AM-003
Status last verified
Aug 2023
First submitted
3 Oct 2019
Last updated
14 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Yes: De-identified individual participant data that underlie the results of this study may be shared.

Publications

  • 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.

    PubMed 32819975

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Echopulse and Poly ICLC in people with Melanoma and Breast Cancer, run by Craig L Slingluff, Jr at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 51 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Unable to enroll enough patients to complete targeted enrollment in a reasonable time.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess the safety and toxicity of FUSA administered alone or in combination with PD-1 antibody blockade. (time frame: 30 days after the last study intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04116320, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2025.

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