Using Niraparib for Maintenance Treatment in Uterine Serous Carcinoma

Trial of Maintenance With Niraparib in Patients With Stage III, Stage IV or Platinum-sensitive Recurrent Uterine Serous Carcinoma

This study is testing if the drug Niraparib can help people with advanced uterine serous carcinoma stay in remission after responding to previous chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Northwell Health (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 5 sites (New Brunswick, New Jersey and 4 other locations)
• Trial ID: NCT04080284 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of Niraparib as a maintenance treatment for patients with advanced or platinum-sensitive recurrent uterine serous carcinoma (USC). The study aims to assess both the efficacy and safety of Niraparib in this patient population, which shares genomic similarities with serous ovarian cancer. Eligible participants must have a histologically confirmed diagnosis of USC and have shown a response to prior platinum-based chemotherapy. The trial will involve monitoring patient outcomes following Niraparib treatment to determine its potential benefits.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 and older with a confirmed diagnosis of advanced stage or recurrent platinum-sensitive uterine serous carcinoma.

Not a fit: Patients with non-serous types of endometrial cancer or those who are not platinum-sensitive may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with advanced uterine serous carcinoma.

How similar studies have performed: Previous studies have shown promising results with Niraparib in similar cancer types, suggesting a potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Female, age at least 18 years
2. ECOG performance status of \<2
3. Written voluntary informed consent
4. Histologically diagnosed Uterine Serous Carcinoma.
5. Patient must agree to undergo Foundation One testing.
6. Patient diagnosed with advanced stage USC including stage III, stage IV, or platinum-sensitive recurrent USC
7. 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.
8. Patients eligible if receiving 1st or 2nd line chemotherapy for recurrence.
9. 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.
10. 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.
11. Lesions can be non-measurable or measurable by RECIST 1.1 criteria.
12. Adequate organ function, defined as:

    1. Absolute neutrophil count ≥ 1,500/μL
    2. Platelets ≥ 100,000/μL
    3. Hemoglobin ≥ 9 g/dL
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
    5. Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
    6. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
13. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
14. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
15. 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):

    1. ≥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.
    2. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
    3. Able to take oral medications.

Exclusion Criteria:

* 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

  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.

Where this trial is running

New Brunswick, New Jersey and 4 other locations

• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States (RECRUITING)
• Imbert Cancer Center Northwell Health — Bay Shore, New York, United States (RECRUITING)
• Greenlawn Cancer Institute, Northwell Health — Greenlawn, New York, United States (RECRUITING)
• RJ Zuckerberg Cancer Hospital — New Hyde Park, New York, United States (RECRUITING)
• Cancer Institute at Lenox Hill — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Marina Frimer, MD — Northwell Health
• Study coordinator: Marina Frimer

Conditions: Endometrial Cancer, Papillary Serous Endometrial Carcinoma, Uterine Serous Carcinoma, Endometrial Carcinoma, Cancer of the Endometrium, Niraparib, uterine Cancer, papillary serous uterine cancer