N-Plus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Nord Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Jul 2024 → ongoing

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2022-502559-69-01

ClinicalTrials.gov

NCT05460000

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary aim of this study is to show that the recurrence free survival (RFS) in patients receiving three cycles of chemotherapy followed by maintenance with niraparib is not inferior to 6 cycles of chemotherapy followed by niraparib in advanced HRDpositive high-grade ovarian cancer patients with no residual tumor mass following primary tumor debulking.

Secondary objectives 7

1. Comparison between both arms of the Overall survival
2. Comparison of the time to first subsequent treatment (TFST)
3. Comparison of the time without symptoms of disease or toxicity of treatment
4. Estimation and comparison of progression free survival 2 (PFS2)
5. Estimation and comparison of patient reported outcomes (PRO's)
6. Safety assessments
7. Cost effectiveness

Conditions and MedDRA coding

advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) HRDpositive high-grade ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary with no residual tumor mass following primary tumor debulking

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Written informed consent and obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
2. Female patient, age ≥ 18 years.
3. FIGO Stage III-IV high-grade ovarian cancer (all histological types, except mucinous histology)
4. Complete primary debulked patients (without any macroscopic residuals), confirmed by CT-Scan postoperatively.
5. Patients must have formalin-fixed, paraffin-embedded tumor samples available from the primary cancer for central NGS analysis and must be HRD positive defined as BRCAmut independent of NOGGO GIS Score OR NOGGO GIS Score >83 independent of BRCA status, based on these results
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Patients must be able to take oral medications.
8. Synchronous and secondary malignancies are allowed if the prognosis of the ovarian cancer is not affected. The investigator must contact the medical monitoring team before enrolling the patient in the clinical trial.
9. Patients must have normal organ and bone marrow function: a. Hemoglobin ≥ 10.0 g/dL independent of transfusion ≤ 14 days prior to screening hemoglobin assessment b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L c. Platelet count ≥ 100 x 109/L d. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); < 2 × ULN if hyperbilirubinemia is due to Gilbert’s syndrome e. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2,5 x ULN f. Serum creatinine ≤ 1.5 x institutional ULN and creatinine clearance > 30 mL/min.
10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment. Female patients of childbearing potential must have a negative serum pregnancy test result ≤3 days prior to administration of the first dose of study treatment. Patients are considered to be of childbearing potential unless 1 of the following applies: a. Considered to be permanently sterile. Permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy; or b. Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state. Female patients of reproductive potential must practice highly effective methods (failure rate < 1% per year) of contraception with their partners, if of reproductive potential, during treatment and for 6 months following the last dose of chemotherapy or the last dose of niraparib, whichever occurs later, or longer if requested by local authorities. Highly effective contraception includes: Ongoing use of progesterone only injectable or implantable contraceptives; Placement of an intrauterine device (IUD) or intrauterine system (IUS); Bilateral tubal occlusion; Sexual abstinence as defined as complete or true abstinence, acceptable only when it is the usual and preferred lifestyle of the patient; periodic abstinence (e.g., calendar, symptothermal, post-ovulation methods) is not acceptable; or Sterilization of the male partner, with appropriate post-vasectomy documentation of absence of sperm in ejaculate.

Exclusion criteria 22

1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e., germ cell tumors) and Ovarian tumors of low malignant potential (e.g., borderline tumors), or mucinous carcinoma of the ovary.
2. Low-grade ovarian, fallopian tube or peritoneal cancer.
3. Has known hypersensitivity to any of the study drugs or any of the excipients of any of the study drugs.
4. Has known hypersensitivity to platin-containing compounds other than carboplatin.
5. Patients posttransplant, including previous allogeneic bone marrow transplant.
6. Has undergone interval debulking of the tumor.
7. Has received any anti-cancer therapy for ovarian cancer other than primary surgery.
8. Administration of other simultaneous chemotherapy drugs, any other anti-cancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroidal antiemetics).
9. Has received prior treatment with a PARP inhibitor or has participated in a trial where any treatment arm included the administration of a PARP inhibitor.
10. Bevacizumab is planned to be given together with first line chemotherapy or as maintenance.
11. Clinically significant cardiovascular disease: a. Cerebrovascular accident or myocardial infarction or unstable angina ≤6 months before start of study treatment b. Severe cardiac arrhythmia (recent event or active or uncontrolled) c. New York Heart Association grade ≥2 congestive heart failure d. Uncontrolled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy or posterior reversible encephalopathy syndrome e. History of stroke or transient ischemic attack ≤6 months before start of study treatment f. Coronary/peripheral artery bypass graft ≤6 months before start of study treatment g. Deep vein thrombosis or thromboembolic events ≤1 month before start of study treatment
12. History or evidence of brain metastases or spinal cord compression.
13. Known history of MDS or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/AML.
14. Current, clinically relevant bowel obstruction at the time of randomization.
15. Patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
16. Pregnant or lactating women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (see inclusion criteria) starting with the screening visit through at least 6 months after the last dose of chemotherapy treatment or through at least 1 month after the last dose of niraparib, whichever occurs later.
17. Participation in another clinical study with an investigational product immediately prior to randomization. Earliest time point for randomization is after the time required for the investigational product to undergo 5 half-lives has passed.
18. Has a known history of Human Immunodeficiency Virus (HIV) infection (known HIV1/HIV2 antibodies positive) or acquired immunodeficiency syndrome (AIDS) related illness.
19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] has been detected) infection.
20. Has active infection with SARS-CoV-2 (antigen test).
21. Patient who might be dependent on the sponsor, CRO, site or the investigator.
22. In Germany: Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40a S. 1 Nr. 2 AMG.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. RFS (Recurrence free survival, defined as time from treatment randomization to the earliest date of assessment of first relapse or death by any cause)

Secondary endpoints 7

1. Overall survival (OS) (time to event and rate at 3 and 5 years)
2. Time to first subsequent treatment (TFST)
3. TWIST (Time Without Symptoms of disease progression or Toxicity of treatment) at baseline, 3, 6, and 12 months
4. PFS2 (Time from randomization until the date of second objective disease progression or death by any cause)
5. PROs (EORTC QLQ-C30 and EORTC QLQ-OV28)
6. Safety assessment includes AEs/SAEs, laboratory evaluations, vital signs and physical examination
7. Cost effectiveness

Investigational products

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

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Nord Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Sponsor organisation

Nord Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Address

Schwedenstraße 9, Wedding Wedding

City

Berlin

Postcode

13359

Country

Germany

Scientific contact point

Organisation

Nord Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Contact name

Dr. Maren Keller

Public contact point

Organisation

Nord Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

Contact name

Dr. Maren Keller

Locations

6 EU/EEA countries · 51 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 35 files

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

Application history

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