Phase 2 Randomized Study of Intraperitoneal Radium-224 in Homologous Recombination Proficient Advanced Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

Trial ID: 2023-508497-28-00
Sponsor: Oncoinvent ASA

Trial statistics

science

test molecule

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Metastases to peritoneum

Objectives

The primary objective of this study is 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 cancer with peritoneal metastasis that are homologous recombination (HR) proficient following treatment with Radspherin® versus no treatment. This objective is clinically relevant as it aims to evaluate the efficacy of Radspherin® in delaying disease progression, which is crucial for improving patient outcomes in this population.

Secondary objectives include:

Comparing overall survival (OS) in the same patient population following Radspherin® treatment versus no treatment.
Comparing peritoneal progression-free survival (PPFS) in these patients.
Assessing the time to first subsequent anticancer therapy or death (TFST).
Evaluating the time to second subsequent anticancer therapy or death (TSST).
Comparing changes from baseline in biomarkers, specifically CA125 levels.
Assessing the quality of life (QoL) in patients following treatment.

These secondary objectives are designed to provide a comprehensive evaluation of the potential benefits of Radspherin® beyond progression-free survival, including overall survival, treatment timelines, biomarker changes, and quality of life, which are all important factors in the management of patients with carcinomatosis of the peritoneal cavity.

Participants

The clinical trial involves a total of **49 participants** diagnosed with **carcinomatosis of the peritoneal cavity**. The study population is exclusively female, with an age range of 18 years and older. Participants are required to have a confirmed diagnosis of 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. The selection criteria ensure that participants have completed 3 or 4 cycles of neoadjuvant chemotherapy with either regression or stable disease on diagnostic imaging and are assessed to be operable to R0. Participants must have an Eastern Cooperative Oncology Group Performance Status Score of 0 to 2, indicating they are fit enough to undergo interval debulking surgery and further treatment according to the standard of care. The trial does not include male subjects or vulnerable populations. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to specific contraceptive measures if of childbearing potential. The trial's focus is on comparing progression-free survival following Radspherin® treatment versus no treatment in this specific patient group.

Plans and Procedures

The clinical trial is a **Phase 2**, randomized, open-label, multicenter study designed to evaluate the efficacy of an intraperitoneal **α-emitting radionuclide therapy** using Radspherin in patients with primary advanced high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer with peritoneal metastasis. The primary objective is to compare progression-free survival (PFS) in patients treated with Radspherin versus those receiving no treatment. The trial is expected to commence recruitment in April 2024 and conclude by October 2030.

Participants will be randomly assigned to either the treatment group receiving Radspherin or the control group. The study involves several key visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as confirmed homologous recombination proficiency, adequate organ function, and a suitable performance status. Following randomization, participants will undergo regular follow-up visits to monitor treatment effects and assess primary and secondary endpoints, including overall survival (OS) and changes in biomarkers. The end-of-study visit will mark the completion of the trial for each participant.

The expected duration of participant involvement is contingent upon the individual's response to treatment and disease progression, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The study will utilize computed tomography (CT) or magnetic resonance imaging (MRI) to assess PFS and other endpoints according to the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

Treatment

The clinical trial involves the administration of **Radspherin**, an experimental medication formulated as a **suspension for injection**. The active substance in Radspherin is **radium-224 adsorbed in calcium carbonate microparticles**. This pharmaceutical preparation is intended for **intraperitoneal use**. The dosing regimen specifies a maximum daily dose of 7 MBq (megabecquerel) and a total maximum dose of 7 MBq, administered over a treatment period of one day. The administration of Radspherin is designed to deliver targeted **α-emitting radionuclide therapy** to 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.

In this study, Radspherin is compared against a control group receiving no treatment, serving as the non-experimental arm of the trial. This design allows for the evaluation of progression-free survival (PFS) in patients receiving the experimental therapy versus those who do not receive any additional treatment beyond the standard-of-care, which includes neoadjuvant chemotherapy and interval debulking surgery. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol and to assess the safety and efficacy of the treatment.

Efficacy

Efficacy in this clinical trial will be assessed primarily through **Progression-Free Survival (PFS)**, defined as the time from randomization until the date of first progression or death, whichever occurs first. PFS will be evaluated using computed tomography (CT) or magnetic resonance imaging (MRI) and according to the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Secondary endpoints include **Overall Survival (OS)**, defined as the time from the date of randomization until death from any cause, and **Peritoneal Progression-Free Survival (PPFS)**, which is the time from randomization until the first progression in the peritoneum or death from any cause, assessed similarly using CT/MRI and RECIST v1.1.

Additional secondary endpoints include **Time to First Subsequent Therapy (TFST)** and **Time to Second Subsequent Therapy (TSST)**, both defined as the time from randomization to the date of first or second subsequent anticancer therapy or death from any cause, respectively. Changes in the biomarker **CA125** and patient-reported outcome scores using the Quality of Life (QoL) forms from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OV28 will also be measured. These assessments will provide a comprehensive evaluation of the treatment's efficacy in patients with primary advanced high-grade serous or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer with peritoneal metastasis.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Able and willing to provide written informed consent and to comply with the clinical study protocol (CSP).
Adequate hepatic function: 1) Serum bilirubin < 1.5 x upper limit of normal (ULN), and 2) Aspartate transaminase and alanine transaminase ≤ 3 x ULN.
Adequate bone marrow function: 1) Absolute neutrophil count ≥ 1.0 x 10^9/l, and 2) Platelets ≥ 100 x 10^9/l, and 3) Haemoglobin ≥ 9 g/dL.
For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment.
For females of childbearing potential agreement to use at least one of the following highly effective (failure rate < 1%) methods of contraception during the treatment period and for at least 9 months if they receive Radspherin®, unless hysterectomy or oophorectomy is performed during IDS. 1) Total abstinence (when this is in line with the preferred and usual lifestyle of the patient), periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 2) Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before enrolment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment. 3) Use of oral (oestrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Note: 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 enrolment.
Female of age ≥ 18 years.
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 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.
HR-proficient tumour based on available testing, or HR result inconclusive, provided there are no known somatic or germline BRCA1/2 mutations.
Received NACT (numbers of cycles as per investigator’s discretion) with regress or stable disease on diagnostic imaging and assessed to be operable to R0 pre-surgery.
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 renal function: Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 40 ml/min or measured creatinine clearance ≥ 40 ml/min.

cancel

Exclusion Criteria

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 NACT.
Pregnant or lactating (nursing) women.
Active infections requiring antibiotics, and/or physician monitoring, or recurrent fever > 38.0 ⁰C 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 enrolment.
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.