Phase 2, randomised study of Radspherin® in patients with primary advanced epithelial cancer with peritoneal metastasis that are homologous recombination proficient and scheduled to undergo neoadjuvant chemotherapy and interval debulking surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oncoinvent Solutions AS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Jun 2024 → ongoing

Decision date (initial)

2024-04-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

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 Radspherin® treatment versus no treatment.

Secondary objectives 6

1. To compare overall survival (OS) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient following Radspherin® treatment versus no treatment.
2. To compare peritoneal PFS (PPFS) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient following Radspherin® treatment versus no treatment.
3. 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 following Radspherin® treatment versus no treatment.
4. 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 following Radspherin® treatment versus no treatment.
5. To compare change from baseline in biomarkers (CA125) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient following Radspherin® treatment versus no treatment.
6. To compare Quality of Life (QoL) in patients with primary advanced epithelial cancer with peritoneal metastasis that are HR proficient following Radspherin® treatment versus no treatment.

Conditions and MedDRA coding

Carcinomatosis of peritoneal cavity

Regulatory references

Scientific advice from competent authorities

Norwegian Medicines Agency, Food And Drug Administration, European 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. Adequate hepatic function: 1) Serum bilirubin < 1.5 x upper limit of normal (ULN), and 2) Aspartate transaminase and alanine transaminase ≤ 3 x ULN.
3. 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.
4. For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment.
5. 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.
6. Female of age ≥ 18 years.
7. 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).
8. Peritoneal and other metastases eligible for IDS to no residual tumour.
9. Adverse events recovered to at least Grade 1 from the effects (excluding alopecia) of any prior medical therapy for malignancy.
10. HR-proficient tumour based on available testing, or HR result inconclusive, provided there are no known somatic or germline BRCA1/2 mutations.
11. 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.
12. 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.
13. Adequate renal function: Calculated creatinine clearance using the Cockcroft-Gault formula ≥ 40 ml/min or measured creatinine clearance ≥ 40 ml/min.

Exclusion criteria 17

1. Confirmed HR deficient.
2. Suspicion of peritoneal leak, shunt, or otherwise suspected atypical target compartment pharmacokinetics, based on investigator’s judgement, patient history and diagnostic images.
3. 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.
4. Symptomatic central nervous system metastasis.
5. 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).
6. Prior abdominal/pelvic radiotherapy.
7. Disease progression during NACT.
8. Pregnant or lactating (nursing) women.
9. Active infections requiring antibiotics, and/or physician monitoring, or recurrent fever > 38.0 ⁰C associated with a clinical diagnosis of active infection.
10. Active liver disease with positive serology for active hepatitis B, hepatitis C or known human immunodeficiency virus (HIV).
11. Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease.
12. 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.
13. 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.
14. Administration of an investigational medicinal product within 4 weeks, or at least 5 times the half-life, prior to enrolment.
15. Concurrent administration of any cancer therapy other than planned study treatment within 4 weeks prior to, and up to 4 weeks after the surgery.
16. Treatment with bevacizumab within 5 weeks prior to IDS.
17. Known hypersensitivity to any of the excipients of the study drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS defined as time from randomisation until the date of first progression or death, whichever occurs first. PFS will be assessed using computed tomography (CT) or magnetic resonance imaging (MRI) and according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

Secondary endpoints 6

1. OS defined as time from date of randomisation until the date of death from any cause.
2. PPFS defined as the date from randomisation until the date of first progression in the peritoneum or death for any cause, whichever occurs first. PPFS will be assessed using CT/MRI and according to RECIST v1.1.
3. TFST defined as the time from the date of randomisation until the date of first subsequent anticancer therapy or death from any cause, whichever occurs first. Planned post-operative chemotherapy and planned maintenance therapy is considered as a part of the primary treatment and should not be assessed as new subsequent anticancer therapy.
4. TSST defined as the time from the date of randomisation to the date of second subsequent anticancer therapy or death from any cause, whichever occurs first. Planned post-operative chemotherapy and planned maintenance therapy is considered as a part of the primary treatment and should not be assessed as new subsequent anticancer therapy.
5. Change in biomarker (CA125).
6. Changes from baseline in patient reported outcome scores using QoL forms European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ- OV28.

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 4

Locations

4 EU/EEA countries · 9 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 68 files

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

Application history

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