Actinium Therapy for Late-stage Aggressive Sarcomas

What this study is about

The goal of this clinical trial is to learn about the safety of drug \[Ac225\]RTX-2358 and the diagnostic imaging agent \[Cu64\]LNTH-1363S. Additionally Ratio Therapeutics will learn if \[Ac225\]RTX-2358 drug is effective in treating advanced sarcoma. The main questions the study aims to answer in Phase/Part 1 of the trial are: * Is \[Ac225\]RTX-2358 tolerable or does it cause toxicities (medical problems) in patients. * What is the most tolerable dose of \[Ac225\]RTX-2358 * Does the treatment show effectiveness on advanced sarcoma Participants will: * Take drug \[Ac225\]RTX-2358 once every 8 weeks (4 cycle target; 6 cycle maximum) over a period of 12 months * Visit the clinic three times for the first week of cycle one, then once a week for the remaining 7 weeks of cycle 1 for check-ups and tests. * For cycles 2-6: patient will visit the clinic once every 2 weeks for checkups and tests * Remain in long term follow-up for a period of four additional years

Who can join (things the study team will check)

✅ You may be able to join if…

• 18 years of age or older.
• History of relapse and refractory soft tissue sarcoma.
  • Histological confirmation of sarcoma at any point since diagnosis
  • At least 1 prior treatment regimen
• Measurable disease as per RECIST (v1.1) for soft tissue sarcoma that is also positive on FAPi PET/CT or PET/MRI scan.
• ECOG performance status of 0 or 1.
• Adequate Organ reserve and renal function as evidenced by:
  • Neutrophil count ≥ 1200 µL without granulocyte colony stimulating factor
  • Platelet count ≥ 100,000 µL
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin level ≤ 1.5 × upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
  • Calculated creatinine clearance ≥ 60 mL/min. 6. Coagulation parameters (prothrombin time, international normalized ratio and activated partial thromboplastin time) ≤ 1.5 × ULN 7. All patients (males and females of childbearing potential) must agree to practice 2 forms of highly effective contraceptive precautions to prevent pregnancy from the time consent is signed and throughout the trial.
  • The patient or the patient's legal representative must be willing and able to provide written informed consent.

🚫 You may not be able to join if…

• History of whole pelvic irradiation.
• History of radioligand therapy.
• Treatment within 14 days prior to first administration with:
  • Palliative surgery or external beam radiation.
  • Approved anticancer therapy including chemotherapy or immunotherapy.
  • Any investigational therapy.
  • Any major surgery (e.g., requiring general anesthesia).
• Patients who are scheduled for external beam radiation therapy or radioligand therapy during the study period.
• Congestive heart failure > Class II New York Heart Association Functional Classification, current pericarditis, myocardial infarction within 6 months, or symptomatic coronary artery disease.
• Patients with uncontrollable incontinence.
• Unstable or clinically significant concurrent medical condition that would, in the opinion of the Investigator, jeopardize the safety of a patient and/or their compliance with the protocol.
• Active infection requiring systemic antibacterial/antibiotic, antifungal, or antiviral therapy. Chronic antiviral therapy for stable viral disease can be included.
• History of active fibrotic condition.
• Any active malignancy other than sarcoma that requires treatment.
• Stable brain metastasis is allowed but documented untreated metastases to brain or meninges are excluded.
• Currently pregnant or lactating.
• Known allergy to any of the study drugs or their excipients.
• Inability or unwillingness to comply with any of the required imaging studies or study assessments.

Where this trial is running

• UCLA, Los Angeles, California, United States
• Mayo Clinic, Rochester, Minnesota, United States
• Memorial Sloane Kettering Cancer Center, New York, New York, United States
• Case Western, Cleveland, Ohio, United States
• MD Anderson Cancer Center, Houston, Texas, United States
• Princess Margaret Cancer Centre, Toronto, Ontario, Canada