Clinical Trial 23176

• Overview

  Study Title:

  A Phase 2, randomised, open label, multicentre study of an intraperitoneal alpha-emitting radionuclide therapy (Radspherin®) in patients with primary advanced high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, with peritoneal metastasis that are homologous recombination proficient and scheduled to undergo neoadjuvant chemotherapy and interval debulking surgery

  Summary:

  Phase 2, controlled, randomised, parallel assignment, open label, multicentre study to evaluate efficacy and safety of a single intraperitoneal injection of Radspherin® in patients with primary advanced high-grade serous or high-grade endometrioid epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, with peritoneal metastasis that are HR proficient and scheduled to undergo Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS).

  Objective:

  Primary objective: * To compare progression free survival (PFS) in patients with primary advanced high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer1 with peritoneal metastasis that are homologous recombination (HR) proficient and scheduled to undergo neoadjuvant chemotherapy (NACT), interval debulking surgery (IDS) and Radspherin® versus NACT and IDS. Secondary objectives: * To compare overall survival (OS) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient and scheduled to undergo NACT, IDS and Radspherin® versus NACT and IDS. * To compare peritoneal PFS (PPFS) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient and scheduled to undergo NACT, IDS and Radspherin® versus NACT and IDS. * To compare time to first subsequent anticancer therapy or death (TFST) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient and scheduled to undergo NACT, IDS and Radspherin® versus NACT and IDS. * To compare time to second subsequent anticancer therapy or death (TSST) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient and scheduled to undergo NACT, IDS and Radspherin® versus NACT and IDS. * To compare change from baseline in biomarkers (CA125) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient and scheduled to undergo NACT, IDS and Radspherin® versus NACT and IDS. * To compare Quality of Life (QoL) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient and scheduled to undergo NACT, IDS and Radspherin® versus NACT and IDS.

• Treatments

  Therapies:

  Radiotherapy; Surgery; Therapy (NOS)

  Medications:

  Radspherin ()

• Inclusion Criteria

  Inclusion Criteria:
  • Able and willing to provide written informed consent and to comply with the clinical study protocol (CSP).
  • Female 18 years of age or older.
  • Patients with primary advanced high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer (FIGO Stage IIIB/C or IV).
  • Peritoneal and other metastases eligible for interval debulking surgery (IDS) to no residual tumour.
  • Adverse events recovered to at least Grade 1 from the effects (excluding alopecia) of any prior medical therapy for malignancy.
  • Confirmed HR proficient by Myriad MyChoice CDx testing.
  • Completed 3 or 4 cycles of Neoadjuvant chemotherapy (NACT) with regress or stable disease on diagnostic imaging and assessed to be operable to R0.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 to 2 and patient fit enough to undergo IDS and further treatment according to standard of care.
  • Adequate organ function.
  • For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
  • For females of childbearing potential agreement to use at least one of the following highly effective (failure rate > In addition to the use of one highly effective method of contraception as listed above, a condom is required for all male partners during the treatment period and for at least 9 months after the dose of IMP, unless vasectomised at least 6 months prior to enrollment.

• Exclusion Criteria

  Exclusion Criteria:
  • Known somatic or germline BRCA1 or BRCA2 mutations or confirmed HR deficient.
  • Suspicion of peritoneal leak, shunt, or otherwise suspected atypical target compartment pharmacokinetics, based on investigator's judgement, patient history and diagnostic images.
  • Epithelial borderline tumours, ovarian clear cell carcinoma, mucinous ovarian carcinoma, malignant Brenner tumours, non-epithelial ovarian malignancies, carcinosarcoma and neuroendocrine tumours or recurrent ovarian cancer.
  • Symptomatic central nervous system metastasis.
  • Another primary malignancy within the past 3 years (except for non melanoma skin cancer, cutaneous melanoma stage 1, cervical cancer in situ or FIGO 2023 Stage IA1 or IA3 prior or synchronous endometrial cancer).
  • Prior abdominal/pelvic radiotherapy.
  • Disease progression during 3 to 4 cycles of NACT.
  • Pregnant or lactating (nursing) women.
  • Active infections requiring antibiotics, and/or physician monitoring, or recurrent fever > 38.0 degrees C associated with a clinical diagnosis of active infection.
  • Active liver disease with positive serology for active hepatitis B, hepatitis C or known human immunodeficiency virus (HIV).
  • Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease.
  • Any condition or illness that, in the opinion of the investigator or the medical monitor, would compromise the safety of the patients or interfere with the evaluation of the safety of the investigational medicinal product.
  • In the investigator's opinion not able to comply with study procedures. Any medical or psychological condition that would preclude participation in the study or compromise the ability to give informed consent.
  • Administration of an investigational medicinal product within 4 weeks, or at least 5 times the half life, prior to enrollment.
  • Concurrent administration of any cancer therapy other than planned study treatment within 4 weeks prior to, and up to 4 weeks after the surgery.
  • Treatment with bevacizumab within 5 weeks prior to IDS.
  • Known hypersensitivity to any of the excipients of the study drug.

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