Niraparib in High-grade Endometrial Cancer Trial

NCT ID: NCT05289648

Last Updated: 2024-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

EARLY_PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-01

Study Completion Date

2026-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Endometrial Cancer Serous Adenocarcinoma Uterine Neoplasm

Keywords

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Biomarker Chemotherapy naïve Synthetic lethality Phase 0

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Preoperative Niraparib

Single 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.

Group Type EXPERIMENTAL

Niraparib oral capsule

Intervention Type DRUG

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

Interventions

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Niraparib oral capsule

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

Intervention Type DRUG

Other Intervention Names

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Zejula

Eligibility Criteria

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Inclusion Criteria

1. 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
2. Histological and staging criteria:

Patients must have histologically diagnosed
1. 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.
2. Grade 2 endometrioid carcinoma with abnormal TP53 by immunohistochemistry.
3. Surgical criteria: patients with operable disease are eligible
4. 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.
5. 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.
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Patients must have adequate organ function, defined as follows:

1. Absolute neutrophil count ≥ 1,500/µL
2. Platelets ≥ 100,000/µL
3. Hemoglobin ≥ 10 g/dL
4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation
5. Total bilirubin ≤ 1.5 x ULN
6. Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 x ULN
8. Patients must be able to take oral medications

Exclusion Criteria

1. Histology:

1. Grade 1 endometrioid carcinoma OR
2. Grade 2 endometrioid carcinoma with wild type TP53 OR
3. Grade 2 endometrioid carcinoma with an unknown TP53 status
2. 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
* the original endometrial biopsy tissue block does not contain sufficient tumor tissue
3. Patient is pregnant, breastfeeding, or expecting to conceive children, while receiving study treatment and for 3 months after the last dose of study treatment;
4. Patient has a known hypersensitivity to the components of niraparib or its excipients;
5. Patient is simultaneously enrolled in any clinical trial of niraparib or any other investigational therapy;
6. Patient has had any known ≥Grade 3 anemia, neutropenia or thrombocytopenia due to any prior medication that persisted \>4 weeks;
7. Patient has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myelocytic anemia (AML);
8. 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;
9. 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:

1. Patient received a transfusion (platelets or red blood cells) within 2 weeks of the first dose of study treatment;
2. 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.
10. 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.
11. 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.
12. Patient is immunocompromised (patients with splenectomy are allowed).
13. Patient has known, active hepatic disease (ie, hepatitis B or C).
14. 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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Sir Mortimer B. Davis - Jewish General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Shannon Salvador

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shannon Salvador, MD MSc

Role: PRINCIPAL_INVESTIGATOR

McGill University, Jewish General Hospital

Walter Gotlieb, MD PhD

Role: PRINCIPAL_INVESTIGATOR

McGill University, Jewish General Hospital

References

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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.

Reference Type BACKGROUND
PMID: 30413523 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31388127 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27717299 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32988624 (View on PubMed)

Other Identifiers

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301014

Identifier Type: -

Identifier Source: org_study_id