Endometrial CancerPhase 2NCT04080284
Trial of Maintenance With Niraparib- Uterine Serous Carcinoma
A Phase 2 study testing Niraparib in people with Endometrial Cancer and Papillary Serous Endometrial Carcinoma, run by Northwell Health at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer, Papillary Serous Endometrial Carcinoma, Uterine Serous Carcinoma
- What is being tested?
- Niraparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 6 sitesUnited States
- Study dates
- 30 Dec 2019to 1 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 24Show fewer
- 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
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
- Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
- Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
- Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
- Female participant has a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non childbearing potential. Non childbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 6.4 for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
- Able to take oral medications.
Who cannot join
- 1. Participant must not be simultaneously enrolled in any interventional clinical trial
- 2. Drainage of ascites during the last 2 cycles of last chemotherapy
- 3. 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.
- 4. Persistent >Grade 2 anemia, neutropenia, or thrombocytopenia from prior cancer therapy, that has persisted > 4 weeks and was related to the most recent treatment.
- 5. Symptomatic uncontrolled brain or leptomeningeal metastases.
- 6. Known hypersensitivity to the components of Niraparib
Show all 16Show fewer
- 7. Major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery
- 8. 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)
- 9. Patient considered a poor medical risk due to serious, uncontrolled medical disorder, non-malignant systemic disease or active uncontrolled infection.
- 10. Patients must not have received a transfusion within 4 weeks of the first dose of study treatment
- 11. 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.
- 12. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
- 13. Immunocompromised patients (splenectomy patients are allowed)
- 14. Patients with known active hepatitis disease
- 15. Prior treatment with a known PARP inhibitor
- 16. Patients noted to have MSI-H mutational burden.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Imbert Cancer Center Northwell Health
Bay Shore, New York, 11706
Greenlawn Cancer Institute, Northwell Health
Greenlawn, New York, 11740
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 07103
RJ Zuckerberg Cancer Hospital
New Hyde Park, New York, 11042
Cancer Institute at Lenox Hill
New York, New York, 10075
Rutgers NJ School of Medicine
Newark, New Jersey, 07103
About this study
Official title: Trial of Maintenance With Niraparib in Patients With Stage III, Stage IV or Platinum-sensitive Recurrent Uterine Serous Carcinoma
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.
Read the detailed description
Uterine serous carcinoma (USC) accounts for up to 40% of endometrial cancer-related deaths. In contrast to the more common endometrioid histology, USC is more likely to present in advanced stage and carries a worse prognosis. USC mimics the most common serous carcinoma of the ovary and has high probability for nodal and intra-peritoneal spread. Furthermore, studies have indicated that USC harbors a high frequency of somatic TP53 mutations, germline BRCA1 mutations, and mutations within the Fanconi Anemia - BRCA pathway. Data is supportive of the USC association with hereditary breast and ovarian cancer, essentially harboring mutations in DNA repair genes. Approximately 5% of women with USC have germline mutations in 3 different tumor suppressor genes including BRCA1, CHEK2, and TP53.(1,2) The Cancer Genome Atlas Research network reported 4 groups of endometrial tumors based on integrated genomic data - including a novel POLE subtype in 10% endometrial tumors. Patients with uterine serous cancers shared many similar characteristics with basal-like breast and high grade serous ovarian cancers, suggesting a correlation with "BRCAness".(3)
Given the "BRCAness" of USC, recent multicenter prospective cohort study of 1083 women with BRCA1 and BRCA2 mutations who underwent risk reducing salpingo-oophorectomies (RRSO) without hysterectomy were noted to have increased serous/serous-like endometrial carcinoma if they harbored BRCA1 mutations.(4) The study recommended to consider this risk of uterine cancer when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1 women. This further supports the high rates of mutations noted among USC patients. A recent systematic review and meta-analysis support the view that USC is a component of BRCA 1/2 -associated tumors. Furthermore, this analysis supports that women with USC should be offered screening for germline mutations when there is a positive family history of malignancies associated with hereditary breast and ovarian cancer syndrome(HBOCS).(5) Furthermore, the Cancer Genome Atlas Research network reported 4 groups of endometrial tumors based on integrated genomic data - including a novel POLE subtype in 10% endometrial tumors. Patients with uterine serous cancers shared many similar characteristics with basal-like breast and high grade serous ovarian cancers, suggesting a correlation with "BRCAness".(3)
Poly(ADP-ribose) polymerases (PARP1 and PARP2) play an important role in DNA repair. Upon formation of DNA breaks, PARP binds at the end of broken DNA strands helping in DNA repair of damage. The hypothesis is that treatment with PARP inhibitors will allow the killing of a subset of cancer cells with deficiencies in DNA repair pathways. For example, a tumor harboring a BRCA or Homologous Recombination gene mutation will have selective blockage by PARP inhibitors in order to maintain genomic integrity. Furthermore, the data in serous ovarian cancer has indicated that tumors arising in a non-BRCA patient that has a homologous recombination deficiency could also enhance tumor cell sensitivity to PARP inhibitors.
PARP inhibitors (PARPi) are synthetically lethal to tumor cells with homologous recombination deficiency (HRD). HRD leads to common phenotype of genome-wide loss of heterozygosity (LOH). Recent analysis of the ARIEL2 part 1 in platinum sensitive ovarian cancer trial found that patients with germline or somatic BRCA mutation or wild-type BRCA with high LOH had longer progression-free survival and improved responses with rucaparib treatment than did patients with wild-type BRCA and low LOH.(7)
The rationale for this current trial is based on significant clinical and genomic similarities of USC and epithelial ovarian carcinomas.(1,2,4) Currently the treatment for stage III and IV USC yields approximately 20-30% survival at 2 years and 10%-20% survival at 3-5 years post diagnosis with current standard therapy of chemotherapy +/-radiation depending on the sites of the disease at surgical staging/debulking. Furthermore, there is no successful second line therapy for patients with recurrent USC and no available clinical trials for patients with recurrent disease. Given the most recent findings of the multi-national, Phase 3 NOVA trial in women with platinum sensitive, recurrent ovarian cancer, Niraparib significantly prolonged the median progression-free survival - irrespective of the presence or absence of a germline BRCA mutation or the presence/absence of a homologous recombinant deficiency.(6) The investigators hypothesize that patients receiving Niraparib maintenance in addition to standard therapy for USC may lead to improved progression free survival in women with suboptimally debulked stage III, stage IV, and platinum-sensitive recurrent USC. The investigators hypothesize that this treatment will be well tolerated in this group of patients.
- Conditions
- Endometrial Cancer, Papillary Serous Endometrial Carcinoma, Uterine Serous Carcinoma, Endometrial Carcinoma, Cancer of the Endometrium
- Being tested
- Niraparib
- Keywords
- Niraparib, uterine Cancer, papillary serous uterine cancer, endometrial cancer, serous uterine cancer, Endometrial, Endometrial Carcinoma, Recurrent Uterine Carcinoma, platinum-sensitive
- Medical subject headings
- Endometrial Neoplasms, Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called ZEJULA
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.
| Study group | Role | What they receive |
|---|---|---|
| Niraparib | Experimental | Oral niraparib
-Cohort - Uterine serous carcinoma Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1 year
Secondary outcomes (6)
PFS
Progression-free survival (PFS)
Measured: 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
To further describe safety and assess toxicities encountered with the use of the proposed treatment regimen in patients with stage III, all stage IV, or recurrent uterine serous carcinoma (USC).
Measured: 5 years
Mutational burden
To identify the prevalence of somatic mutations, HRD mutations, and overall mutational burden in patients with USC and classify tumor into loss of heterozygosity (LOH) high and low phenotype.
Measured: 3 years
Quality of Life (QOL) measures using Functional Assessment of Cancer Therapy (FACT- endometrial cancer) and EQ-5D-5L Euroqol
To evaluate quality of life (QOL) for the subjects undergoing this treatment, using validated tools. QOL will be assessed every 3 months during treatment course. [Functional Assessment of Cancer Therapy - Endometrial Cancer questionnaire (score range from 0 to 120 - Higher scores represent better quality of life. EQ-5D-5L Euroqol is scored 0-20, with negative values corresponding to death, full health, and health states worse than death
Measured: 5 years
Overall Survival
Overall Survival
Measured: 3 years
ORR
Overall response rate (ORR) at 2, and 3 years interval from start of treatment protocol
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2019
- Study start30 Dec 2019
- Primary completion1 Jan 2025
- Study completion1 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Collaborators
- Tesaro, Inc.
- Responsible party
- Principal investigator, Marina Frimer, Northwell Health
- Investigators
- Marina Frimer, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04080284
- Sponsor's protocol ID
- 19-0380
- Status last verified
- Aug 2025
- First submitted
- 15 Aug 2019
- Last updated
- 19 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual Participant Data will be available to other researchers via REDCAP, with de-identified source documents uploaded by the site. Remote review of the CRFs will be done monthly, cross-checking with source documents. Clarification of administrative matters will be performed by study coordinator and research manager. Remote monitoring of specific data will include eligibility, adverse events, tumor response, and protocol compliance. Data will be maintained in a password- protected secure database, secured on an ePHI. The database will contain a study identifier that is linked to the subject's medical record number. To maintain confidentiality of identifiable information, paper based records will be kept in a secured location only available to research personnel, computer based files will be made available to research personnel through the use of access privileges and passwords, and whenever feasible identifiers will be removed from study information.
Publications
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.
PubMed 22811390Frimer 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.
PubMed 27016235Cancer 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.
PubMed 23636398Shu 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.
PubMed 27367496de 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.
PubMed 28049106Mirza 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.
PubMed 27717299Swisher 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.
PubMed 27908594Takeuchi 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.
PubMed 35443252
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Maintenance With Niraparib in Patients With Stage III, Stage IV or Platinum-sensitive Recurrent Uterine Serous Carcinoma
- ClinicalTrials.gov ID
- NCT04080284
- Acronym / sponsor ID
- 19-0380
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Collaborators
- Tesaro, Inc.
- Study start
- 30 Dec 2019 (actual)
- Primary completion
- 1 Jan 2025 (actual)
- Study completion
- 1 Jan 2025 (actual)
- First posted
- 6 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Uterine serous carcinoma (USC) accounts for up to 40% of endometrial cancer-related deaths. In contrast to the more common endometrioid histology, USC is more likely to present in advanced stage and carries a worse prognosis. USC mimics the most common serous carcinoma of the ovary and has high probability for nodal and intra-peritoneal spread. Furthermore, studies have indicated that USC harbors a high frequency of somatic TP53 mutations, germline BRCA1 mutations, and mutations within the Fanconi Anemia - BRCA pathway. Data is supportive of the USC association with hereditary breast and ovarian cancer, essentially harboring mutations in DNA repair genes. Approximately 5% of women with USC have germline mutations in 3 different tumor suppressor genes including BRCA1, CHEK2, and TP53.(1,2) The Cancer Genome Atlas Research network reported 4 groups of endometrial tumors based on integrated genomic data - including a novel POLE subtype in 10% endometrial tumors. Patients with uterine serous cancers shared many similar characteristics with basal-like breast and high grade serous ovarian cancers, suggesting a correlation with "BRCAness".(3)
Given the "BRCAness" of USC, recent multicenter prospective cohort study of 1083 women with BRCA1 and BRCA2 mutations who underwent risk reducing salpingo-oophorectomies (RRSO) without hysterectomy were noted to have increased serous/serous-like endometrial carcinoma if they harbored BRCA1 mutations.(4) The study recommended to consider this risk of uterine cancer when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1 women. This further supports the high rates of mutations noted among USC patients. A recent systematic review and meta-analysis support the view that USC is a component of BRCA 1/2 -associated tumors. Furthermore, this analysis supports that women with USC should be offered screening for germline mutations when there is a positive family history of malignancies associated with hereditary breast and ovarian cancer syndrome(HBOCS).(5) Furthermore, the Cancer Genome Atlas Research network reported 4 groups of endometrial tumors based on integrated genomic data - including a novel POLE subtype in 10% endometrial tumors. Patients with uterine serous cancers shared many similar characteristics with basal-like breast and high grade serous ovarian cancers, suggesting a correlation with "BRCAness".(3)
Poly(ADP-ribose) polymerases (PARP1 and PARP2) play an important role in DNA repair. Upon formation of DNA breaks, PARP binds at the end of broken DNA strands helping in DNA repair of damage. The hypothesis is that treatment with PARP inhibitors will allow the killing of a subset of cancer cells with deficiencies in DNA repair pathways. For example, a tumor harboring a BRCA or Homologous Recombination gene mutation will have selective blockage by PARP inhibitors in order to maintain genomic integrity. Furthermore, the data in serous ovarian cancer has indicated that tumors arising in a non-BRCA patient that has a homologous recombination deficiency could also enhance tumor cell sensitivity to PARP inhibitors.
PARP inhibitors (PARPi) are synthetically lethal to tumor cells with homologous recombination deficiency (HRD). HRD leads to common phenotype of genome-wide loss of heterozygosity (LOH). Recent analysis of the ARIEL2 part 1 in platinum sensitive ovarian cancer trial found that patients with germline or somatic BRCA mutation or wild-type BRCA with high LOH had longer progression-free survival and improved responses with rucaparib treatment than did patients with wild-type BRCA and low LOH.(7)
The rationale for this current trial is based on significant clinical and genomic similarities of USC and epithelial ovarian carcinomas.(1,2,4) Currently the treatment for stage III and IV USC yields approximately 20-30% survival at 2 years and 10%-20% survival at 3-5 years post diagnosis with current standard therapy of chemotherapy +/-radiation depending on the sites of the disease at surgical staging/debulking. Furthermore, there is no successful second line therapy for patients with recurrent USC and no available clinical trials for patients with recurrent disease. Given the most recent findings of the multi-national, Phase 3 NOVA trial in women with platinum sensitive, recurrent ovarian cancer, Niraparib significantly prolonged the median progression-free survival - irrespective of the presence or absence of a germline BRCA mutation or the presence/absence of a homologous recombinant deficiency.(6) The investigators hypothesize that patients receiving Niraparib maintenance in addition to standard therapy for USC may lead to improved progression free survival in women with suboptimally debulked stage III, stage IV, and platinum-sensitive recurrent USC. The investigators hypothesize that this treatment will be well tolerated in this group of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Niraparib | Experimental | Drug: NiraparibOral niraparib -Cohort - Uterine serous carcinoma |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (16 listed)
- 1. Participant must not be simultaneously enrolled in any interventional clinical trial
- 2. Drainage of ascites during the last 2 cycles of last chemotherapy
- 3. 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.
- 4. Persistent >Grade 2 anemia, neutropenia, or thrombocytopenia from prior cancer therapy, that has persisted > 4 weeks and was related to the most recent treatment.
- 5. Symptomatic uncontrolled brain or leptomeningeal metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZEJULAStudy 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. | Drug | Niraparib |
Primary outcome
PFS
Time frame: 1 year
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).
6 secondary outcomes
PFS
Time frame: 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 5 years
Mutational burden
Time frame: 3 years
Quality of Life (QOL) measures using Functional Assessment of Cancer Therapy (FACT- endometrial cancer) and EQ-5D-5L Euroqol
Time frame: 5 years
Overall Survival
Time frame: 3 years
ORR
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2025.
- Background: PubMed 22811390Pennington 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.
- Background: PubMed 27016235Frimer 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.
- Background: PubMed 23636398Cancer 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.
- Background: PubMed 27367496Shu 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.
- Background: PubMed 28049106de 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.
- Background: PubMed 27717299Mirza 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.
- Background: PubMed 27908594Swisher 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.
- Derived from this study: PubMed 35443252Takeuchi 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.
- Individual participant dataSharing planned: No. Individual Participant Data will be available to other researchers via REDCAP, with de-identified source documents uploaded by the site. Remote review of the CRFs will be done monthly, cross-checking with source documents. Clarification of administrative matters will be performed by study coordinator and research manager. Remote monitoring of specific data will include eligibility, adverse events, tumor response, and protocol compliance. Data will be maintained in a password- protected secure database, secured on an ePHI. The database will contain a study identifier that is linked to the subject's medical record number. To maintain confidentiality of identifiable information, paper based records will be kept in a secured location only available to research personnel, computer based files will be made available to research personnel through the use of access privileges and passwords, and whenever feasible identifiers will be removed from study information.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marina Frimer, MD principal investigator
Northwell Health
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib in people with Endometrial Cancer and Papillary Serous Endometrial Carcinoma, run by Northwell Health at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04080284, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2025.