Trial of Maintenance With Niraparib- Uterine Serous Carcinoma

NCT04080284 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 19-0380
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 6

Brief Summary

Uterine serous carcinoma (USC) accounts for up to 40% of endometrial cancer-related deaths. Patients with USC share many genomic and clinical characteristics with patients who has serous ovarian cancer. The objective of this study is to evaluate the efficacy of maintenance Niraparib regimen in patients with advanced or platinum sensitive recurrent uterine serous carcinoma. Additionally, the investigators aim to further describe the safety of this regimen. The investigators hypothesize that Niraparib maintenance will be a well-tolerated treatment and show significant response in patients with uterine serous carcinoma.

Conditions

Endometrial Cancer; Papillary Serous Endometrial Carcinoma; Uterine Serous Carcinoma; Endometrial Carcinoma; Cancer of the Endometrium

Keywords

Niraparib; uterine Cancer; papillary serous uterine cancer; endometrial cancer; serous uterine cancer; Endometrial; Endometrial Carcinoma; Recurrent Uterine Carcinoma; platinum-sensitive

Outcome Measures

Primary Outcomes (1)

• PFS

  To determine the Progression Free Survival (PFS) at 1 year in the proposed Niraparib regimen in the population of patients with stage III, all stage IV, or recurrent uterine serous carcinoma (USC).

  1 year

Secondary Outcomes (6)

• PFS

  3 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  5 years

• Mutational burden

  3 years

• Quality of Life (QOL) measures using Functional Assessment of Cancer Therapy (FACT- endometrial cancer) and EQ-5D-5L Euroqol

  5 years

• Overall Survival

  3 years

Study Arms (1)

Niraparib

EXPERIMENTAL

Oral niraparib -Cohort - Uterine serous carcinoma

Drug: Niraparib

Interventions

Niraparib DRUG

Study treatment will be administered orally Q day continuously. Up to three capsules of 100mg strength will be taken at each dose administration. Initiation dose will be defined per current FDA guidelines for Niraparib treatment in ovarian cancer. Dose interruption (no longer than 28 days) will be allowed. Dose reduction will be allowed based on treatment side effects. Dose reductions to 2 capsules daily (200mg) and subsequently to 1 capsule daily (100mg) will be allowed. No further dose reductions will be allowed. The timing of efficacy or safety evaluations should not be affected by dose interruptions or reductions.

Also known as: ZEJULA

Niraparib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, age at least 18 years
• ECOG performance status of \<2
• Written voluntary informed consent
• Histologically diagnosed Uterine Serous Carcinoma.
• Patient must agree to undergo Foundation One testing.
• Patient diagnosed with advanced stage USC including stage III, stage IV, or platinum-sensitive recurrent USC
• If recurrent USC, patient must have platinum sensitive disease after initial treatment; defined as achieving a response (CR or PR) and disease progression \>6 months after completion of their last dose of platinum chemotherapy.
• Patients eligible if receiving 1st or 2nd line chemotherapy for recurrence.
• The patient must have achieved a partial, stable, or complete tumor response following the last chemotherapy (minimal of 3 cycles) regimen of physician choice chemotherapy indicating partial, stable, complete tumor response.
• Patients must receive Niraparib maintenance within 12 weeks after completion of their final dose of chemotherapy regimen or within 14 weeks if received radiation therapy. CT Chest/Abd/Pelvis will be performed within 28 days of starting Niraparib.
• Lesions can be non-measurable or measurable by RECIST 1.1 criteria.
• Adequate organ function, defined as:
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• \. Participant must not be simultaneously enrolled in any interventional clinical trial
• \. Drainage of ascites during the last 2 cycles of last chemotherapy
• \. Radiotherapy was given within 2 weeks encompassing \>20% of the bone marrow or any radiation therapy within one week prior to Day 1 of protocol therapy. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior to initiating protocol therapy.
• \. Persistent \>Grade 2 anemia, neutropenia, or thrombocytopenia from prior cancer therapy, that has persisted \> 4 weeks and was related to the most recent treatment.
• \. Symptomatic uncontrolled brain or leptomeningeal metastases.
• \. Known hypersensitivity to the components of Niraparib
• \. Major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery
• \. Diagnosis, detection, or treatment of invasive cancer other than uterine cancer \</= 2 years prior to study enrollment (except basal or squamous cell carcinoma of the skin that has been definitively treated)
• \. Patient considered a poor medical risk due to serious, uncontrolled medical disorder, non-malignant systemic disease or active uncontrolled infection.
• \. Patients must not have received a transfusion within 4 weeks of the first dose of study treatment
• \. Participant must not have received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
• \. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• \. Immunocompromised patients (splenectomy patients are allowed)
• \. Patients with known active hepatitis disease
• \. Prior treatment with a known PARP inhibitor

Sponsors & Collaborators

• Northwell Health: lead
• Tesaro, Inc.: collaborator

Study Sites (6)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 07103, United States

Location

Rutgers NJ School of Medicine

Newark, New Jersey, 07103, United States

Location

Imbert Cancer Center Northwell Health

Bay Shore, New York, 11706, United States

Location

Greenlawn Cancer Institute, Northwell Health

Greenlawn, New York, 11740, United States

Location

RJ Zuckerberg Cancer Hospital

New Hyde Park, New York, 11042, United States

Location

Cancer Institute at Lenox Hill

New York, New York, 10075, United States

Location

Related Publications (8)

• Pennington KP, Walsh T, Lee M, Pennil C, Novetsky AP, Agnew KJ, Thornton A, Garcia R, Mutch D, King MC, Goodfellow P, Swisher EM. BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. Cancer. 2013 Jan 15;119(2):332-8. doi: 10.1002/cncr.27720. Epub 2012 Jul 18.

  PMID: 22811390 BACKGROUND

• Frimer M, Levano KS, Rodriguez-Gabin A, Wang Y, Goldberg GL, Horwitz SB, Hou JY. Germline mutations of the DNA repair pathways in uterine serous carcinoma. Gynecol Oncol. 2016 Apr;141(1):101-7. doi: 10.1016/j.ygyno.2015.12.034.

  PMID: 27016235 BACKGROUND

• Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Integrated genomic characterization of endometrial carcinoma. Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113.

  PMID: 23636398 BACKGROUND

• Shu CA, Pike MC, Jotwani AR, Friebel TM, Soslow RA, Levine DA, Nathanson KL, Konner JA, Arnold AG, Bogomolniy F, Dao F, Olvera N, Bancroft EK, Goldfrank DJ, Stadler ZK, Robson ME, Brown CL, Leitao MM Jr, Abu-Rustum NR, Aghajanian CA, Blum JL, Neuhausen SL, Garber JE, Daly MB, Isaacs C, Eeles RA, Ganz PA, Barakat RR, Offit K, Domchek SM, Rebbeck TR, Kauff ND. Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations. JAMA Oncol. 2016 Nov 1;2(11):1434-1440. doi: 10.1001/jamaoncol.2016.1820.

  PMID: 27367496 BACKGROUND

• de Jonge MM, Mooyaart AL, Vreeswijk MP, de Kroon CD, van Wezel T, van Asperen CJ, Smit VT, Dekkers OM, Bosse T. Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report. Eur J Cancer. 2017 Feb;72:215-225. doi: 10.1016/j.ejca.2016.11.028. Epub 2016 Dec 31.

  PMID: 28049106 BACKGROUND

• Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Madry R, Christensen RD, Berek JS, Dorum A, Tinker AV, du Bois A, Gonzalez-Martin A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7.

  PMID: 27717299 BACKGROUND

• Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. doi: 10.1016/S1470-2045(16)30559-9. Epub 2016 Nov 29.

  PMID: 27908594 BACKGROUND

• Takeuchi H, Miyamoto T, Fuseya C, Asaka R, Ida K, Ono M, Tanaka Y, Shinagawa M, Ando H, Asaka S, Shiozawa T. PIM1 is a Poor Prognostic Factor for and Potential Therapeutic Target in Serous Carcinoma of the Endometrium. Int J Gynecol Pathol. 2023 May 1;42(3):282-292. doi: 10.1097/PGP.0000000000000882. Epub 2022 Apr 12.

  PMID: 35443252 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Uterine Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Marina Frimer, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Niraparib maintenance treatment will be given to patients for 1 year on study or until disease progression. Patients not tolerating the treatment will stop the niraparib treatment based on criteria described below. Patients who are benefitting from treatment will have access to their assigned treatment as long as considered acceptable by their treating physician or until they are discontinued for one of the below reasons.

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: September 6, 2019
• Study Start: December 30, 2019
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)