Radium-224 adsorbed in calcium carbonate microparticles for Peritoneal carcinomatosis | Colorectal carcinoma

Inclusion criteria

• {"criterion_text":"- Able and willing to provide written informed consent and to comply with the clinical study protocol (CSP)."}
• {"criterion_text":"- For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment."}
• {"criterion_text":"- 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®: 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."}
• {"criterion_text":"- For non-sterile males whose female partner is of childbearing potential: agreement to use condom during the treatment period and for at least 6 months if they received Radspherin®. The female partner should use at least one of the following highly effective (failure rate < 1%) methods of contraception during the same period: 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 been stable on the same pill for a minimum of 3 months before taking study treatment."}
• {"criterion_text":"- Non-sterile males must agree to refrain from donating sperm for the entire treatment period and for up to 6 months after the dose of IMP."}
• {"criterion_text":"- Age ≥ 18 years."}
• {"criterion_text":"- Histologically confirmed colorectal carcinoma. In case of recurrent metastatic disease from colorectal carcinoma to the peritoneal cavity, where the clinical diagnosis seems clear, a confirmative frozen section biopsy of the peritoneal metastases (consistent with metastasis from colorectal carcinoma) during surgery is acceptable."}
• {"criterion_text":"- Peritoneal metastases eligible for cytoreductive surgery where resection to no residual tumour (CC-0) is deemed to be achievable."}
• {"criterion_text":"- AEs recovered to at least Grade 1 from the effects (excluding alopecia) of any prior medical therapy for malignancy."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 to 1"}
• {"criterion_text":"- Adequate renal function: Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 40 ml/min or measured creatinine clearance ≥ 40 ml/min."}
• {"criterion_text":"- Adequate hepatic function: 1) Serum bilirubin < 1.5 x upper limit of normal (ULN), and 2) Aspartate transaminase and alanine transaminase ≤ 3 x ULN."}
• {"criterion_text":"- Adequate bone marrow function: 1) Absolute neutrophil count ≥ 1.0 x 10^9/l, and 2) Platelets ≥ 100 x 10^9/l, and 3) Hemoglobin ≥ 9 g/dL."}

Exclusion criteria

• {"criterion_text":"- Presence of peritoneal metastasis originating from appendix vermiformis, other synchronous metastatic lesions, symptomatic central nervous system metastases. Suspicion of non-regional (e.g. retroperitoneal, thoracic) metastatic lymph nodes on imaging."}
• {"criterion_text":"- Any condition or illness that, in the opinion of the investigator or the medical monitor, would compromise the safety of the patient or interfere with the evaluation of the safety of the investigational medicinal product."}
• {"criterion_text":"- Any patient who, in the investigator’s opinion, was not able to comply with study procedures. Presence of any medical or psychological condition that would preclude participation in the study or compromise the ability of the patient to give informed consent."}
• {"criterion_text":"- Known hypersensitivity to any of the excipients in the study drug."}
• {"criterion_text":"- Rectal carcinoma previously treated with pelvic radiation."}
• {"criterion_text":"- Suspicion of peritoneal leak, shunt, or otherwise suspected atypical target compartment pharmacokinetics, based on investigator’s judgement, patient history and diagnostic images."}
• {"criterion_text":"- Pregnant or lactating (nursing) women."}
• {"criterion_text":"- Active infections requiring antibiotics and/or physician monitoring, or recurrent fever >38.0 °C associated with a clinical diagnosis of active infection."}
• {"criterion_text":"- Administration of an investigational medicinal product within 4 weeks or at least 5 times the half-life of the product, prior to enrolment."}
• {"criterion_text":"- Concurrent administration of any other cancer therapy other than the planned study treatment within 4 weeks prior to and up to 4 weeks after the surgery."}
• {"criterion_text":"- Another primary malignancy within the past 3 years (except for non-melanoma skin cancer, cutaneous melanoma stage 1, cervical cancer in situ, or in situ Stage 1 synchronous endometrial cancer)."}
• {"criterion_text":"- Concurrent congestive heart failure or prior history of New York Heart Association Class III/IV cardiac disease."}

Primary endpoints

• {"endpoint_text":"- PFS defined as time from date of randomisation until the date of first progression or death, whichever occurs first. PFS will be assessed using CT/MRI and according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.","definition_or_measurement_approach":"PFS defined as time from date of randomisation until the date of first progression or death, whichever occurs first; assessed using CT/MRI and according to RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- OS defined as time from date of randomisation until the date of death from any cause.","definition_or_measurement_approach":"Overall survival measured as time from randomisation until death from any cause."}
• {"endpoint_text":"- PPFS defined as time from date from randomisation until the date of first progression in the peritoneum or death from any cause, whichever occurs first. PPFS will be assessed using CT/MRI and according to RECIST v1.1.","definition_or_measurement_approach":"Peritoneal progression-free survival measured from randomisation to first peritoneal progression or death; assessed by CT/MRI per RECIST v1.1."}
• {"endpoint_text":"- Change in biomarkers (CEA, CA19-9 and CA125).","definition_or_measurement_approach":"Change from baseline in serum biomarkers carcinoembryonic antigen (CEA), CA19-9 and CA125."}
• {"endpoint_text":"- Changes from baseline in patient reported outcome scores using QoL forms European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ- CR29.","definition_or_measurement_approach":"Patient-reported quality of life assessed using EORTC QLQ-C30 and QLQ-CR29 questionnaires; changes from baseline will be analysed."}
• {"endpoint_text":"- Incidence, relatedness, severity and seriousness of AEs as characterised using the latest version of National Cancer Institute Common Terminology Criteria version 5.0 for AEs (NCI CTCAE)","definition_or_measurement_approach":"Adverse events characterised by incidence, relatedness, severity and seriousness using NCI CTCAE v5.0."}
• {"endpoint_text":"- Changes from baseline in laboratory values (haematology, serum biochemistry and urine analyses), vital signs (heart rate and systolic/diastolic blood pressure), and body weight","definition_or_measurement_approach":"Laboratory and vital sign changes assessed as change from baseline in hematology, biochemistry, urine analyses, heart rate, blood pressure and body weight."}
• {"endpoint_text":"- Proportion of patients with documented surgical complications according to Clavien-Dindo-Slankamenac classification during the treatment period (Day 1 to 29) and until 1 year after the date of randomisation.","definition_or_measurement_approach":"Surgical complications classified by Clavien-Dindo-Slankamenac during Day 1–29 and up to 1 year post-randomisation; reported as proportion of patients."}
• {"endpoint_text":"- Incidence, relatedness, severity and seriousness of AESIs as characterised using the NCI CTCAE version 5.0.","definition_or_measurement_approach":"Adverse events of special interest characterised by incidence, relatedness, severity and seriousness using NCI CTCAE v5.0."}

Norway

Earliest CTIS Part Ii Submission Date

12-03-2024

Latest Decision Or Authorization Date

26-02-2026

Processing Time Days

716

Number Of Sites

1

Number Of Participants

25

Sweden

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

717

Number Of Sites

1

Number Of Participants

20

Netherlands

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

717

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Oncoinvent Solutions AS

Organisation Type

Pharmaceutical company

Country Of Registered Address

Norway

Third parties

• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Preparation of Part 2 documents","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}