A Study of Niraparib in Combination With Abemaciclib for Late Line Treatment of Ovarian Cancer (NICHOL TRIAL)

NCT06594679 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NICHOL INT 124/23
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

This is an interventional trial. The goal of this clinical trial is dose finding. There are two phases: phase Ib to determine the MTD and recommended phase II dose of niraparib in combination with abemaciclib in patients with advanced ovarian cancer. Target population will be patients (woman, age \> 18 years) with epithelial ovarian, fallopian tube or peritoneal cancer treated with at least 2 lines of therapy.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• dose finding

  This is a dose-escalation study of niraparib plus abemaciclib followed by an efficacy study for late-line treatment of ovarian cancer

  18 months

• dose finding, phase Ib clinical trial

  Maximum tolerated dose (MTD) of niraparib in combination with abemaciclib in patients with advanced ovarian cancer defined as the dose level immediately below the dose at which ≥ 33% of patients experience dose-limiting toxicity as defined by protocol according to CTCAE 5.0

  From enrollment to the end of phase 1

• PART II: Disease control rate at 16 weeks (DCR16wks):

  proportion of patients whose disease shrinks (i.e. complete or partial response) or remains stable over 16 weeks after the start of niraparib + abemaciclib combination. Revised RECIST 1.1 criteria will be used to assess tumor response

  From enrollment of first patient of part II to to the 16-week-radiologic assessment of last patient

Study Arms (1)

ARM 1

EXPERIMENTAL

Niraparib+Abemaciclib

Drug: Niraparib Tosylate Monohydrate

Interventions

Niraparib Tosylate Monohydrate DRUG

Combination of niraparib and abemaciclib

Also known as: Abemaciclib

ARM 1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has read and understands the informed consent form and has given written informed consent prior to any study procedures.
• Age \> 18 years
• Life expectancy of at least 3 months
• Histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube cancer
• Confirmed recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer for which there is no known or established treatment available with curative intent.
• Able to provide archived tumor tissue;(formalin fixed-paraffin embedded (FFPE) tumor sample or a minimum of 20 unstained slides is required for study eligibility.
• NOTE: if archived tissue is not available, patient must be willing to undergo a tumor biopsy at screening if medically feasible.
• Patients must have completed at least 2 previous chemotherapy regimens for platinum sensitive disease (\> 6 months). Patients must have completed their last therapy regimen \> 4 weeks prior to treatment initiation and have radiological confirm of progression disease.
• Patients could have received maintenance therapy with a PARPi, but they must remain sensitive to platinum-based chemotherapy, based on the radiological or CA-125 response to their most recent course of platinum-based chemotherapy (carboplatin, cisplatin or oxaliplatin) or have demonstrated progressive disease while taking a PARP inhibitor as a previous therapy. Response to prior PARP inhibitor is not required.
• Prior PARP therapy could have been administered as either treatment for recurrent disease or as maintenance following prior treatment.
• Patients must have or agree to undergo tumor HRD testing and somatic BRCAmut status testing at screening.
• Patients must agree to undergo blood samples during screening and at the end of treatment for cytogenetic analysis.
• Phase 2 patients only: presence of measurable disease according to RECIST v1.1 criteria as assessed locally by Investigators.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1.
• Absolute neutrophil count (ANC) ≥ 1500/L (within 14 days of study drugs initiation).

You may not qualify if:

• Any other prior therapy directed at the malignant tumor, including immunologic agents administered within 4 weeks prior to first dose of study drug
• Major surgical procedures ≤ 28 days of beginning study treatment, or minor surgical procedures \< 7 days. No timeline window required for port-a-cath placement.
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.
• History of any ≥ grade 3 hematological toxicity due to prior chemotherapy that persisted for more than 4 weeks.
• Patient has uncontrolled hypertension according to CTCAE v. 5.0
• Grade \> 1 toxicity from prior therapy (except alopecia or anorexia) that contraindicates start of new treatment.
• Patient has inability to swallow oral medications or patients with gastrointestinal disorders likely to interfere with absorption of the study medication. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN).
• Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 28 days after treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrollment.
• Chronic assumption of drugs or other products with a narrow therapeutic index and known to be CYP3A4 substrates, or drugs or other products known to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to day -3 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Co-administration of aprepitant or fosaprepitant during this study is prohibited.
• Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to: St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng, grapefruit and seville orange. Patients should stop using these herbal medications at least 7 days prior to first dose of study treatment.
• Any known hypersensitivity or contraindication to the components of the study drugs.
• Any of the following cardiac diseases currently or within the last 6 months: a. Unstable angina pectoris; b. Congestive heart failure; c. Acute myocardial infarction; d. Conduction abnormality not controlled with pacemaker or medication; e. Significant ventricular or supraventricular arrhythmias (patients with chronic rate- controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Evidence of corrected QT interval (specifically QTc calculated using the Fridericia formula \[QTcF\]) \> 470 msec from a single electrocardiogram (ECG) performed at study entry or congenital or acquired long QT syndrome.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• GlaxoSmithKline: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Milano, 20133, Italy

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: September 19, 2024
• Study Start: September 26, 2024
• Primary Completion (Estimated): March 20, 2027
• Study Completion (Estimated): September 18, 2027
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)