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Trial of Maintenance With Niraparib- Uterine Serous Carcinoma

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ClinicalTrials.gov Identifier: NCT04080284
Recruitment Status : Recruiting
First Posted : September 6, 2019
Last Update Posted : March 3, 2020
Sponsor:
Collaborator:
Tesaro, Inc.
Information provided by (Responsible Party):
Marina Frimer, Northwell Health

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.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Papillary Serous Endometrial Carcinoma Uterine Serous Carcinoma Endometrial Carcinoma Cancer of the Endometrium Drug: Niraparib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Trial of Maintenance With Niraparib in Patients With Stage III, Stage IV or Platinum-sensitive Recurrent Uterine Serous Carcinoma
Actual Study Start Date : December 30, 2019
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2025


Arm Intervention/treatment
Experimental: Niraparib

Oral niraparib

-Cohort - Uterine serous carcinoma

Drug: Niraparib
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.
Other Name: ZEJULA




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. PFS [ Time Frame: 3 years ]
    Progression-free survival (PFS)

  2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 5 years ]
    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).

  3. Mutational burden [ Time Frame: 3 years ]
    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.

  4. Quality of Life (QOL) measures using Functional Assessment of Cancer Therapy (FACT- endometrial cancer) and EQ-5D-5L Euroqol [ Time Frame: 5 years ]
    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

  5. Overall Survival [ Time Frame: 3 years ]
    Overall Survival

  6. ORR [ Time Frame: 3 years ]
    Overall response rate (ORR) at 2, and 3 years interval from start of treatment protocol



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04080284


Contacts
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Contact: Sally Flores 516-734-8916 sflores3@northwell.edu
Contact: Mary Agnes Templeton 516-734-8979 mtempleton@northwell.edu

Locations
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United States, New York
Monter Cancer Institute Recruiting
New Hyde Park, New York, United States, 11042
Contact: Mary A Templeton    516-734-8979    MTempleton@northwell.edu   
Contact: Sally Flores    516-734-8916    sflores3@northwell.edu   
Sponsors and Collaborators
Northwell Health
Tesaro, Inc.
Investigators
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Principal Investigator: Marina Frimer, MD Northwell Health
Publications:

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Responsible Party: Marina Frimer, Principle Investigator, Northwell Health
ClinicalTrials.gov Identifier: NCT04080284    
Other Study ID Numbers: 19-0380
First Posted: September 6, 2019    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

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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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Marina Frimer, Northwell Health:
Niraparib
uterine Cancer
papillary serous uterine cancer
endometrial cancer
serous uterine cancer
Endometrial
Endometrial Carcinoma
Recurrent Uterine Carcinoma
platinum-sensitive
Additional relevant MeSH terms:
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Carcinoma
Endometrial Neoplasms
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Cystadenocarcinoma
Adenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents