A Phase 1/2a Study to Evaluate the Dose, Safety and Tolerability and Efficacy of an Intraperitoneal α-emitting Radionuclide Therapy (Radspherin®) in Subjects With Peritoneal Carcinomatosis From Colorectal Carcinoma Following Hyperthermic Intraperitoneal Chemotherapy
Overview
- Phase
- Phase 1
- Intervention
- Radspherin
- Conditions
- Peritoneal Carcinoma
- Sponsor
- Oncoinvent AS
- Enrollment
- 47
- Locations
- 2
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
This is a phase 1/2a open label study to evaluate the dose, safety, tolerability and efficacy of an IP α-emitting radionuclide therapy (Radspherin®) in subjects with peritoneal carcinomatosis (PC) from colorectal carcinoma following complete CRS (cytoreduction score CC-0) and HIPEC.
The study consists of three different cohorts:
- Dose escalation cohorts
- Repeated injection cohorts
- Expansion cohort
Detailed Description
Primary objectives: * To investigate safety and toxicity of Radspherin® * To determine the maximum-tolerated dose (MTD) of Radspherin®, among the four suggested doses 1, 2, 4 and 7 MBq, as a single intraperitoneal (IP) injection and two repeated IP injections following cytoreductive surgery (CRS) and hyperthermic IP chemotherapy (HIPEC) Secondary objectives: * To establish a recommended dose of Radspherin® as a single IP injection and two repeated IP injections following CRS and HIPEC * To describe the biodistribution of Radspherin® * To examine the efficacy and clinical benefit of Radspherin® following CRS and HIPEC Exploratory objectives: * To explore the association of biomarkers with activity/clinical benefits, adverse events (AEs), or other effects associated with Radspherin® * To explore effects of catheter placement, Radspherin® administration technique, and infusion volume on the distribution of 224Ra labelled micro particles in the peritoneal cavity The maximum number of subjects receiving Radspherin® in this study is 67. Subjects who discontinue prior to Radspherin® administration will be replaced. Dose escalation cohorts: 3 - 24 subjects Repeated injection cohorts: 3 subjects Expansion cohort: up to 40 subjects
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able and willing to provide written informed consent and to comply with the clinical study protocol
- •Age ≥ 18 years
- •Histologically confirmed colorectal carcinoma
- •Peritoneal metastases (PCI≤20 assessed during surgery), and histologically confirmed as peritoneal carcinomatosis) eligible for cytoreductive surgery and HIPEC treatment that reaches CC-0 at the end of the surgical procedure
- •AEs recovered to at least grade 1 from the effects (excluding alopecia) of any prior medical therapy for malignancy at time of first administration of Radspherin®
- •ECOG Performance Status Score of 0 - 1
- •Adequate renal function
- •Creatinine ≤ 1.8 mg/dl (159 μmol/l) and
- •Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 45 ml/min, or
- •Measured creatinine clearance ≥ 45 ml/min
Exclusion Criteria
- •Peritoneal metastasis originating from appendix vermiformis. Other synchronous visceral metastatic lesions in liver or lungs, symptomatic central nervous system (CNS) metastases. Metastatic lymph nodes or thoracic lymph nodes
- •Resection or suture of the diaphragm (assessed during surgery)
- •Pregnant or lactating (nursing) women
- •Active infections requiring antibiotics and/or physician monitoring, or recurrent fever \>38.0⁰C associated with a clinical diagnosis of active infection
- •Active liver disease with positive serology for active hepatitis B, hepatitis C or known HIV
- •Administration of an investigational medicinal product within 28 days or at least 5 times the half-life
- •Concurrent administration of any other cancer therapy other within 4 weeks prior to, and up to 4 weeks after the last study treatment
- •Another primary malignancy within the past 3 years (except for non-melanoma skin cancer, cervical cancer in situ or in situ stage 1 synchronous endometrial cancer)
- •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 subjects or interfere with the evaluation of the safety of the IMP
Arms & Interventions
Radspherin
Intervention: Radspherin
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: 21 Days
To determine the maximum-tolerated dose (MTD) of Radspherin®, among the four suggested doses 1, 2, 4 and 7 MBq, as a single intraperitoneal (IP) injection and two repeated IP injections following cytoreductive surgery (CRS) and hyperthermic IP chemotherapy (HIPEC)
Number of participants with Dose Limiting Toxicities as assessed by CTCAE v5.0.
Time Frame: 18 months
To investigate safety and toxicity of Radspherin®
Explore efficacy (expansion cohort)
Time Frame: 18 months
Peritoneal recurrence free survival