Clinical trial NCT05323253: A Clinical Study to Assess the Efficacy and Safety of Alpha DaRT224 for the Treatment of Patients With Recurrent Cutaneous Squamous Cell Carcinoma
Official title: A Prospective International Multicenter, Pivotal, Single Arm, Open Label Clinical Study to Assess the Efficacy and Safety of Intratumoral Alpha DaRT224 for the Treatment of Patients With Recurrent Cutaneous Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Recurrent Squamous Cell Carcinoma
Keywords: Squamous Cell Carcinoma
Recurrent Squamous Cell Carcinoma
Alpha emitting radiation
Carcinoma, Squamous
Skin Cancer
Brachytherapy
Lead sponsor: Alpha Tau Medical LTD.
Sponsor class: INDUSTRY
First posted: 2022-04-12
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an International Multicenter, Pivotal, Single Arm, Open Label pivotal trial with DaRT for the treatment of Recurrent Cutaneous Squamous Cell Carcinoma
Primary purpose: TREATMENT

Brief summary: This is a multi-center clinical study enrolling up to 86 participants. The primary objectives are to determine the objective response rate (ORR) established by the confirmed best overall response (BOR) following intratumoral administration of DaRT - Diffusing Alpha-Emitters Radiation Therapy, as well as to assess the Duration of Response (DOR) 6 months from initial response. Secondary objectives are to assess the safety of DaRT, and to assess the progression free survival (PFS), overall survival (OS), Overall Duration of Response (O-DOR), local control and quality of life (QOL) for patients treated with DaRT.

Detailed description: This study is a prospective multicenter, pivotal, single arm, open label clinical study to assess the efficacy and safety of intratumoral Alpha DaRT-224 for the treatment of patients with recurrent cutaneous squamous cell carcinoma.

The "Diffusing Alpha-emitter Radiation Therapy (DaRT)", based on the interstitial intratumoral placement of an encapsulated Radium-224 source (3.7 days half-life), is described in this study. These sources release short-lived alpha-emitting atoms into the tumor microenvironment by recoil. DaRT seeds will be inserted into recurrent Squamous Cell Carcinoma (SCC) tumors and will be removed following 14-21 days.

The Objective Response Rate (ORR) will be determined based on the confirmed Best Overall Response (BOR) following DaRT insertion. Duration of Response (DOR) will be assessed for up to 6 months from initial response is documented. Safety will be assessed based on the cumulative incidence rate, severity and outcome of device related Adverse Events (AEs). Classification of AEs will be done according to CTCAE v5.

Eligibility criteria: Inclusion Criteria:

1. Patients with recurrent cutaneous SCC histologically confirmed who have failed at least first line standard of care therapy who are not indicated for surgery and standard radiation therapy, or non alpha radiation brachytherapy technologies, and for whom no curative systemic treatment is available
2. Central histopathological confirmation within 6 months of enrollment provided no tumor treatment occurred between the biopsy and enrollment
3. Measurable disease according to RECIST v 1.1.
4. Ability to undergo a CT scan
5. Tumor size ≤7 cm, at the longest diameter.
6. Single lesion per subject.
7. Targeted lesion must be technically amenable for complete coverage (including margins) by the DaRT seeds.Targets will be deemed technically amenable for complete coverage if there are entry and exit vectors for placement that are not hindered by bone or major vessels or other vital organs (eg. eye).
8. Interstitial implant indication validated by multidisciplinary team.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
10. Life expectancy ≥12 months.
11. Subjects male/ female ≥18.
12. Willing and have the ability to provide signed Informed Consent.
13. Patients, male and female, with reproductive potential (including women who are menopausal for less than a year and not surgically sterilized), must practice acceptable effective methods of birth control, such as barrier methods, condom or diaphragm with spermicide or abstinence. Birth control should be continued for 3 months after the DaRT insertion visit.
14. Women with childbearing potential must provide a negative pregnancy test during the screening period and up to V1, prior to the DaRT insertion procedure.
15. Blood tests values:

    * Leucocytes ≥3000mm3,
    * Absolute neutrophil count ≥1500mm3,
    * Platelets ≥100,000 mm3,
    * Total bilirubin ≤ 1.5xULN (upper limit of normal)
    * Aspartate Aminotransferase (AST) ≤2.5xULN,
    * Serum Glutamic-Oxaloacetic Transaminase (SGOT) ≤2.5xULN,
    * Serum Glutamic-Pyruvic Transaminase (SGPT) ≤2.5xULN,
    * Alkaline Phosphatase ≤2.5xULN.
    * Creatinine ≤ 2.0xULN or Creatinine Clearance ≥60 ml/min.
    * INR (International Normalized Ratio) or Prothrombin time ≤1.5xULN.

Exclusion Criteria:

1. Distant or nodal metastatic disease (according to the TNM \[tumor, nodes , and metastases\] staging system - N+ or M1 patients are excluded).
2. T4 disease or perineural spread of disease
3. Previously untreated cutaneous SCC indicated for surgery or radiation.
4. Mucosal, vulvar, anal and penile SCC.
5. Inability to fully cover the entire volume with DaRT seeds
6. Inability to place DaRT seeds into tumor due to inaccessibility by presence of bones or major vessels or vital organs
7. Inability to undergo a CT scan
8. Patients undergoing systemic immunosuppressive therapy excepting intermittent, brief use of systemic corticosteroids.
9. Patients receiving any of the following within 4 weeks of enrollment:

   1. Antineoplastic systemic chemotherapy or biological therapy
   2. Immunotherapy
   3. Investigational agents other than the study intervention
   4. Radiation therapy
   5. Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial.
10. Longest tumor diameter \>7 cm.
11. Tumor with keratoacanthoma histology.
12. Known hypersensitivity to any component of treatment.
13. Clinically significant cardiovascular disease e.g., cardiac failure of New York Heart Association class III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, history of myocardial infarction in the last 12 months.
14. Any medical or Psychiatric illness, which in the opinion of the investigator would compromise the patient's ability to tolerate treatment and to adhere to the clinical trial protocol.
15. Serious medical comorbidities that, in the opinion of the investigator, may affect subject compliance and/or interpretation of treatment safety or effectiveness.
16. High probability of protocol non-compliance (in opinion of investigator).
17. Volunteers participating in another interventional study in the past 30 days which might conflict with the endpoints of this study or the evaluation of response or toxicity of DaRT.
18. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
19. Patients do not agree to use adequate contraception (vasectomy or barrier method of birth control) prior to study entry and for 3 months after the DaRT insertion visit.
20. Breastfeeding or pregnant women
21. Tattoos or other identifying marks which can not be adequately hidden on digital photos

Primary outcomes:
measure: Objective Response Rate
timeFrame: From Day 14 until 52 weeks
measure: Duration of Response
timeFrame: 6 months from from first demonstration of CR or PR after Alpha DaRT seeds insertion.
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 12 months after DaRT seed insertion
measure: Overall Survival
timeFrame: Up to 12 months following DaRT insertion
measure: Time of Local Control
timeFrame: Up to 12 months following DaRT insertion
measure: Patients Quality of Life Assessment
timeFrame: On 14 days,12 weeks and 52 weeks following DaRT insertion
measure: DaRT-related Adverse Events
timeFrame: Up to 12 months following DaRT insertion
measure: Overall Duration of Response (O-DOR)
timeFrame: Up to 12 months following first reported response
measure: User experience
timeFrame: On Day 0 (DaRT insertion) and Day 14 (+7) (DaRT removal)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Health MD Anderson Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Dignity Health Cancer Institute
state: Arizona
city: Phoenix
country: United States
facility: Alliance Dermatology
state: Arizona
city: Los Angeles
country: United States
facility: UCLA
state: California
city: DeLand
country: United States
facility: Day Star Skin and Cancer Center
state: Florida
city: Delray Beach
country: United States
facility: Integrity Research Clinical Associates
state: Florida
city: Delray Beach
country: United States
facility: Palm beach Dermatology Group
state: Florida
city: Delray Beach
country: United States
facility: Palm Beach Dermatology Group
state: Florida
city: Hollywood
country: United States
facility: Hollywood Dermatology
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Baptist Health South Florida MCI
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: West Palm Beach
country: United States
facility: Beer Dermatology
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Hackensack
country: United States
facility: Schweiger Dermatology Group
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Center
state: New Mexico
city: Cooperstown
country: United States
facility: Bassett Healthcare Network
state: New York
city: Queens
country: United States
facility: Northwell Health
state: New York
city: Rockaway Park
country: United States
facility: New York Medical Skin Solutions
state: New York
city: Smithtown
country: United States
facility: MDCS Dermatology
state: New York
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
city: Houston
country: United States
facility: Gulf Coast Cancer Center
state: Texas
city: Houston
country: United States
facility: University Cancer & Diagnostic Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Bellevue
country: United States
facility: Dermatology of Seattle and Bellevue
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah tikva
country: Israel
facility: Belinson-Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
References: