Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
Craig L Slingluff, Jr
With
Theraclion
Age
18–any
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
1. Age ≥18 years.
2. Advanced solid tumor with measurable disease.
3. Subject must have failed or have contraindication to standard therapies.
* 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.
5. 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.
You may not be if
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.
* Patients with advanced solid malignancy for which PD1 or PDL1 blockade is not FDA-approved.
* Patients with metastatic uveal melanoma
* 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.
7. 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.
8. 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.
9. 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.
10. ECOG performance status 0-2.
11. 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,
* Brain metastases will not be targeted for FUSA treatment.
12. Adequate organ function
13. Ability and willingness to give informed consent.
A subject will be excluded from participating in the trial if the subject:
1. Has received the following medications or treatments at any time within 3 weeks of study day 1:
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)
2. Cytotoxic chemotherapy for cancer
2. Has received the following medications or treatments at any time within 4 weeks of study day 1:
1. Radiation therapy (Note: Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week prior to registration)
2. Allergy desensitization injections
3. 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.
6. Any investigational therapeutic agent (participation in the UVA AM004 clinical trial is permitted)
7. Targeted therapies specific for mutated BRAF or for MEK
8. Live vaccine
3. 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.
4. Is HIV positive or has evidence of active Hepatitis B or C virus with some exceptions.
5. Is currently receiving nitrosoureas or has received this therapy within the preceding 6 weeks
6. 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.
7. Has a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.
8. Has an active infection requiring systemic therapy.
9. Has Class III or IV heart disease as classified according to the New York Heart Association.
10. 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.
11. 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. 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.
Clareo Health | Focused Ultrasound Ablation and PD-1 Antibody Blockade in Advanced Solid Tumors
