Phase 2 randomised study of Radspherin® in patients with peritoneal carcinomatosis from colorectal carcinoma after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oncoinvent Solutions AS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Oncoinvent AS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To compare progression-free survival (PFS) in patients with peritoneal metastasis from colorectal carcinoma (CRC) following Radspherin® treatment versus no treatment.

Secondary objectives 7

1. To compare peritoneal progression-free survival (PPFS) in patients with peritoneal metastasis from CRC following Radspherin® treatment versus no treatment.
2. To compare overall survival (OS) in patients with peritoneal metastasis from CRC following Radspherin® treatment versus no treatment.
3. To compare change from baseline in biomarkers (carcinoembryonic antigen [CEA], cancer antigen 19-9 [CA19-9] and cancer antigen 125 [CA125]) in patients with peritoneal metastasis from CRC following Radspherin® treatment versus no treatment.
4. To compare Quality of Life (QoL) in patients with peritoneal metastasis from CRC following Radspherin® treatment versus no treatment.
5. To compare the safety and tolerability of Radspherin® treatment versus no treatment in patients with peritoneal metastasis from CRC.
6. To compare rates of 30-day and 1-year post-operative complications in patients with peritoneal metastasis from CRC following Radspherin® treatment versus no treatment.
7. To compare the incidence of adverse events of special interest (AESIs) in patients with peritoneal metastasis from CRC following Radspherin® treatment versus no treatment.

Conditions and MedDRA coding

Carcinomatosis of peritoneal cavity

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, European Medicines Agency, Norwegian Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003199-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Able and willing to provide written informed consent and to comply with the clinical study protocol (CSP).
2. Age ≥ 18 years.
3. 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.
4. Peritoneal metastases eligible for cytoreductive surgery where resection to no residual tumour (CC-0) is deemed to be achievable.
5. AEs recovered to at least Grade 1 from the effects (excluding alopecia) of any prior medical therapy for malignancy.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 to 1
7. Adequate renal function: Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 40 ml/min or measured creatinine clearance ≥ 40 ml/min.
8. Adequate hepatic function: 1) Serum bilirubin < 1.5 x upper limit of normal (ULN), and 2) Aspartate transaminase and alanine transaminase ≤ 3 x ULN.
9. 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.
10. For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment.
11. 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.
12. 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 have been stable on the same pill for a minimum of 3 months before taking study treatment.
13. 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.

Exclusion criteria 12

1. 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.
2. Rectal carcinoma previously treated with pelvic radiation.
3. Suspicion of peritoneal leak, shunt, or otherwise suspected atypical target compartment pharmacokinetics, based on investigator’s judgement, patient history and diagnostic images.
4. Pregnant or lactating (nursing) women.
5. Active infections requiring antibiotics and/or physician monitoring, or recurrent fever >38.0 °C associated with a clinical diagnosis of active infection.
6. Administration of an investigational medicinal product within 4 weeks or at least 5 times the half-life of the product, prior to enrolment.
7. 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.
8. 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).
9. Concurrent congestive heart failure or prior history of New York Heart Association Class III/IV cardiac disease.
10. 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.
11. 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.
12. Known hypersensitivity to any of the excipients in the study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. OS defined as time from date of randomisation until the date of death from any cause.
2. 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.
3. Change in biomarkers (CEA, CA19-9 and CA125).
4. 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.
5. 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)
6. Changes from baseline in laboratory values (haematology, serum biochemistry and urine analyses), vital signs (heart rate and systolic/diastolic blood pressure), and body weight
7. 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.
8. Incidence, relatedness, severity and seriousness of AESIs as characterised using the NCI CTCAE version 5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oncoinvent Solutions AS

Sponsor organisation

Oncoinvent Solutions AS

Address

Gullhaugveien 7

City

Oslo

Postcode

0484

Country

Norway

Scientific contact point

Organisation

Oncoinvent Solutions AS

Contact name

Information Desk

Public contact point

Organisation

Oncoinvent Solutions AS

Contact name

Information Desk

Third parties 3

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications