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Endometrial CancerEarly Phase 1NIRECNCT05289648

Niraparib in High-grade Endometrial Cancer Trial

A Early Phase 1 study testing Niraparib oral capsule in people with Endometrial Cancer and Serous Adenocarcinoma, run by Sir Mortimer B. Davis - Jewish General Hospital.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The study will investigate the effect of niraparib on tumor tissue in chemotherapy naïve, newly diagnosed, high-grade endometrial cancer patients. Biomarkers of cognate molecular pathways as well as investigational assays will be used to study the antineoplastic effect of the drug. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Niraparib oral capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 May 2024to 31 Jan 2026
Phase
Early Phase 1
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

  • Patients must be female ≥18 years of age, able to understand the study procedures and agree to participate in the study by providing written informed consent
  • Histological and staging criteria:
  • Patients must have histologically diagnosed
  • Grade 3 endometrioid, serous or clear cell endometrial carcinoma, carcinosarcoma, undifferentiated carcinoma in Stage I-III according to International Federation of Gynecology and Obstetrics (FIGO) classification.
  • Grade 2 endometrioid carcinoma with abnormal TP53 by immunohistochemistry.
  • Surgical criteria: patients with operable disease are eligible
Show all 17Show fewer
  • Patients of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin [hCG]) within 7 days prior to receiving the first dose of niraparib.
  • Patients must be postmenopausal, free from menses for >1 year, surgically sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through 3 months after the last dose of niraparib.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients must have adequate organ function, defined as follows:
  • Absolute neutrophil count ≥ 1,500/µL
  • Platelets ≥ 100,000/µL
  • Hemoglobin ≥ 10 g/dL
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation
  • Total bilirubin ≤ 1.5 x ULN
  • Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 x ULN
  • Patients must be able to take oral medications

Who cannot join

  • Histology:
  • Grade 1 endometrioid carcinoma OR
  • Grade 2 endometrioid carcinoma with wild type TP53 OR
  • Grade 2 endometrioid carcinoma with an unknown TP53 status
  • Patient did not consent for the study biopsy and one of the following:
  • the original endometrial biopsy tissue block could not be assessed by the study site pathologist
Show all 22Show fewer
  • the original endometrial biopsy tissue block does not contain sufficient tumor tissue
  • Patient is pregnant, breastfeeding, or expecting to conceive children, while receiving study treatment and for 3 months after the last dose of study treatment;
  • Patient has a known hypersensitivity to the components of niraparib or its excipients;
  • Patient is simultaneously enrolled in any clinical trial of niraparib or any other investigational therapy;
  • Patient has had any known ≥Grade 3 anemia, neutropenia or thrombocytopenia due to any prior medication that persisted >4 weeks;
  • Patient has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myelocytic anemia (AML);
  • Patient has undergone major surgery (per investigator judgment) within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery;
  • Patient has a condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation for the full duration of the study treatment, including:
  • Patient received a transfusion (platelets or red blood cells) within 2 weeks of the first dose of study treatment;
  • Patient received colony-stimulating factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the first dose of study treatment.
  • Another concurrent invasive neoplastic disease (including ovarian), diagnosis of cancer in the last 5 years (except for non-melanoma skin cancer), patient previously had cancer (> 5 years) but she is not considered cured or still treated.
  • Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection;
  • Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
  • Patient is immunocompromised (patients with splenectomy are allowed).
  • Patient has known, active hepatic disease (ie, hepatitis B or C).
  • Patient has a corrected QT interval (QTc) prolongation > 470 milliseconds at screening; - If a patient has a prolonged QTc interval and the prolongation is deemed to be due to a pacemaker upon investigator evaluation (ie, the patient otherwise has no cardiac abnormalities), then the patient may be eligible to participate in the study following approval of a cardiology specialist.

About this study

Official title: The Molecular and the Clinical Effects of Preoperative Niraparib in Patients with High-grade Endometrial Cancer: Phase 0 Exploratory Trial

The study will investigate the effect of niraparib on tumor tissue in chemotherapy naïve, newly diagnosed, high-grade endometrial cancer patients. Biomarkers of cognate molecular pathways as well as investigational assays will be used to study the antineoplastic effect of the drug.

Read the detailed description

Niraparib is a FDA approved Poly(ADP-ribose) polymerase inhibitor (PARPi) for the treatment of platinum-sensitive ovarian serous carcinoma. The safety profile of niraparib was established in phase III clinical trials. The therapeutic effect of niraparib on serous endometrial carcinoma is now being investigated in several clinical trials. However, the antineoplastic effect and the safety profile of niraparib in chemotherapy naïve high-grade endometrial cancer patients is unknown. By employing a phase 0 exploratory trial design, the investigators will study the niraparib's effect on endometrial cancer in chemotherapy naïve patients using molecular biomarkers as sentinels for the antineoplastic effect. Women diagnosed by endometrial biopsy with high-grade endometrial cancer will receive niraparib for 28 days. Staging surgery will be performed 4-6 weeks after the diagnosis (standard of care). The investigators will use the pre-operative biopsy and the surgical specimen to perform comparative multidimensional analysis of endometrial tumors before and after exposure to niraparib.

Being tested
Niraparib oral capsule
Keywords
Biomarker, Chemotherapy naïve, Synthetic lethality, Phase 0
Medical subject headings
Endometrial Neoplasms, Cystadenocarcinoma, Serous, Uterine Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Niraparib oral capsuleDrug

    Also called Zejula

    Low dose oral niraparib capsules (2 x 100 mg) once a day for 28 days

Study groups in NCT05289648
Study groupRoleWhat they receive
Preoperative NiraparibExperimentalSingle arm. Following the initial assessment and endometrial biopsy the participants will receive niraparib for 28 days. After the treatment period the patients will be surgically staged. All participants will receive the standard of care.
Receives: Drug: Niraparib oral capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Tumor cells proliferation before and after the treatment

    Cancer cell proliferation will be quantitatively assessed using immunohistochemical staining for cell-cycle proteins.

    Ki-67 (MIB) stains nuclei of cells in G1-S-G2 phases of the cell-cycle. The proliferation index will be calculated as percent of tumor positive cells. The primary outcome fold change in proliferation index after exposure to niraparib. The quantification will be done by image analysis software with pathologist supervision.

    Measured: Day 30 (day of surgery)

  2. Cell cycle arrest

    The levels of different cell-cycle related proteins increase and decrease throughout the cell cycle, each having its own expression pattern.

    Tumor specimens will be stained for Cyclin D1, Geminin and p21 proteins. The proportion of positive nuclei of each marker after exposure to niraparib will be estimated. The results will be integrated to study the effect of niraparib on endometrial cancer cells proliferation.

    Measured: Day 30 (day of surgery)

  3. Apoptosis marker

    Cleaved caspase-3 (cCas-3) marks cells that activated the programmed cell-death process. cCas-3 positive tumor cells will be compared before and after the exposure to niraparib.

    Measured: Day 30 (day of surgery)

Secondary outcomes (5)

  1. Endometrial thickness

    Comparison of the thickness of endometrial lining before and after treatment

    Measured: Day 1 and Day 28

  2. CA-125 cancer tumor marker

    Investigation of the effect of preoperative niraparib on CA125 levels in patients with high grade endometrial carcinoma

    Measured: Day 1 and Day 28

  3. Adverse effects of Niraparib

    Assessment of adverse effects of niraparib in chemotherapy naïve patients according to CTCAE 5.0

    Measured: every week from day 1 and 21 days after the surgery

  4. Patient Reported Outcomes - General Oncology

    Patients' well being will be assessed by a validated questionnaire: Functional Assessment of Cancer Therapy - General (FACT-G). https://www.facit.org

    Measured: Day 1 and Day 28

  5. Patient Reported Outcomes - Endometrial Cancer

    Patients' well being will be assessed by a validated questionnaire: Functional Assessment of Cancer Therapy - Endometrial (FACT-en). https://www.facit.org

    Measured: Day 1 and Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2022
  2. Study start1 May 2024 (estimated)
  3. Primary completion31 Oct 2025 (estimated)
  4. Study completion31 Jan 2026 (estimated)

Why it stopped: Unable to obtain funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05289648
Sponsor's protocol ID
301014
Acronym
NIREC
Status last verified
Dec 2024
First submitted
18 Feb 2022
Last updated
19 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • de Jonge MM, Auguste A, van Wijk LM, Schouten PC, Meijers M, Ter Haar NT, Smit VTHBM, Nout RA, Glaire MA, Church DN, Vrieling H, Job B, Boursin Y, de Kroon CD, Rouleau E, Leary A, Vreeswijk MPG, Bosse T. Frequent Homologous Recombination Deficiency in High-grade Endometrial Carcinomas. Clin Cancer Res. 2019 Feb 1;25(3):1087-1097. doi: 10.1158/1078-0432.CCR-18-1443. Epub 2018 Nov 9.

    PubMed 30413523

  • Urick ME, Bell DW. Clinical actionability of molecular targets in endometrial cancer. Nat Rev Cancer. 2019 Sep;19(9):510-521. doi: 10.1038/s41568-019-0177-x. Epub 2019 Aug 6.

    PubMed 31388127

  • 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.

    PubMed 27717299

  • Romero I, Rubio MJ, Medina M, Matias-Guiu X, Santacana M, Schoenenberger JA, Guerra EM, Cortes A, Minig L, Coronado P, Cueva JF, Gomez L, Malfettone A, Sampayo M, Llombart-Cussac A, Poveda A. An olaparib window-of-opportunity trial in patients with early-stage endometrial carcinoma: POLEN study. Gynecol Oncol. 2020 Dec;159(3):721-731. doi: 10.1016/j.ygyno.2020.09.013. Epub 2020 Sep 26.

    PubMed 32988624

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Niraparib oral capsule in people with Endometrial Cancer and Serous Adenocarcinoma, run by Sir Mortimer B. Davis - Jewish General Hospital.

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 17 inclusion and 22 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: withdrawn, as of the sponsor's last update on 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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 was withdrawn before enrolling participants, so there are no results.

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?

Tumor cells proliferation before and after the treatment (time frame: Day 30 (day of surgery)). The study lists 3 primary outcomes in all. 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 NCT05289648, which also lists 4 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 Dec 2024.

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