Abemaciclib and Letrozole in Patients With Estrogen Receptor-positive Rare Ovarian Cancer

NCT05872204 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: S66468
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 12

Brief Summary

The purpose of this study is to assess the efficacy and safety of abemaciclib and letrozole for treatment of estrogen receptor-positive rare ovarian cancer.

Conditions

Low Grade Serous Ovarian Carcinoma; Adult Type Granulosa Cell Tumor

Outcome Measures

Primary Outcomes (2)

• The overall response rate (ORR) of the combination of abemaciclib and letrozole, according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

  RECIST is a standard system to measure how cancer responds to different treatments, including chemotherapy, immunotherapy, and radiation therapy.

  Week 24

• The overall response rate (ORR) of the combination of abemaciclib and letrozole, according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

  RECIST is a standard system to measure how cancer responds to different treatments, including chemotherapy, immunotherapy, and radiation therapy.

  3 years

Secondary Outcomes (7)

• The duration of response (DOR) of the combination of abemaciclib and letrozole in the intention-to-treat (ITT) population at Week 24 and 3 years.

  Week 24 and 3 years

• The clinical benefit rate (CBR) of the combination of abemaciclib and letrozole.

  Week 24 and 3 years

• The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).

  3 years

• Progression-free survival (PFS).

  3 years

• Overall survival (OS).

  3 years

Study Arms (1)

Abemaciclib and letrozole

EXPERIMENTAL

Participants received abemaciclib 150 mg tablet orally twice daily and letrozole tablet 2.5 mg orally once daily until disease progression, unacceptable adverse event(s) or death.

Drug: Abemaciclib; Drug: Letrozole

Interventions

Abemaciclib DRUG

150 mg tablet twice daily

Also known as: Verzenios

Abemaciclib and letrozole

Letrozole DRUG

2.5 mg tablet once daily

Also known as: Femara

Abemaciclib and letrozole

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
• Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
• For Stage 1: only patients where platinum is still an option are eligible with no limitations in prior chemotherapy regimens and a maximum of 2 prior endocrine therapy regimens. For Stage 2: a further 20 patients where platinum is still an option will be included, with no limitations in prior chemotherapy regimens and a maximum of 2 prior endocrine therapy regimens. Fifteen patients where platinum is not an option are allowed with no limitations in prior chemotherapy regimens and maximum of 2 prior endocrine therapy regimens. Patients cannot have received chemotherapy for platinum resistant or refractory disease.
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Patient must have recurrent, measurable disease by RECIST v1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least 1 dimension (longest dimension to be recorded). Each lesion must be ≥10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam or must be ≥20 mm when measured by chest x-ray. Lymph nodes must be \>15 mm in short axis when measured by CT or MRI.
• Pre- and post-treatment tissue biopsy and ct-DNA blood sample are mandatory for translational studies. Tissue from an archival tissue sample or fresh tissue obtained from a core or excisional biopsy of a tumor lesion.
• Patients who were previously treated with letrozole or another aromatase inhibitor are allowed, but capped at 10 patients in each cohort.
• 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.
• Patients must not have remaining ovarian function. In women who have at least one retained ovary, menopause must be confirmed with laboratory confirmation. Women who have ovarian function are eligible but must be placed on hormonal suppression after a negative serum or urine human chorionic gonadotropin (hCG) test.
• Abnormal organ function is permitted. However, patients must have:
• absolute neutrophil count ≥1500/mL
• platelets ≥100.000/mL
• hemoglobin ≥9 g/dL
• estimated creatinine clearance ≥ 45 ml/min as calculated using the method standard for the institution

You may not qualify if:

• For Stage 1: patients where platinum is not an option and platinum refractory patients are not allowed. For Stage 2: patients with platinum refractory disease are not allowed. Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).
• The patient has serious preexisting medical condition(s) that 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 \<30 mL/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).
• Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers (for examples, see the Prohibited Concomitant Medications section).
• Diagnosis of another malignancy within 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
• Patient cannot have previously received a prior cyclin dependent kinase inhibitor (CDKi).
• Known Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection.
• Inability or unwillingness to swallow pills.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
• Active infection requiring intravenous (IV) antibiotics or antifungals, or other uncontrolled recurrent illness requiring hospitalization.
• History of any of the following: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), sudden cardiac arrest.
• Prior hematopoietic stem cell or bone marrow transplantation.
• Known history of brain metastasis(es) that may be considered active (screening imaging of brain is not required unless there is clinical suspicion of brain metastases). Patients with previously treated brain metastases may participate provided that the lesions are stable (without evidence of progression for at least 12 weeks on imaging), there is no evidence of new or enlarging brain metastases.
• Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of goserelin (if applicable).
• Known or possible hypersensitivity to letrozole or abemaciclib or any of their excipients.
• Pre/perimenopausal women with a known hypersensitivity to gnRH (gonadotropin-releasing hormone) agonists.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Kom Op Tegen Kanker: collaborator
• Eli Lilly and Company: collaborator
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator

Study Sites (12)

CHU de Liège

Liège, Liège, 4000, Belgium

RECRUITING

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

Institut De Cancerologie Strasbourg Europe

Strasbourg, Bas-Rhin, 67200, France

RECRUITING

Institut Bergonie

Bordeaux, Gironde, 33000, France

RECRUITING

Institut Universitaire Du Cancer Toulouse-Oncopole

Toulouse, Haute-Garonne, 31059, France

RECRUITING

Institut De Cancerologie De L'Ouest

Saint-Herblain, Loire-Atlantique, 44800, France

RECRUITING

Centre Leon Berard

Lyon, Métropole de Lyon, 69008, France

RECRUITING

Groupe Hospitalier Diaconesses Croix Saint Simon

Paris, Île-de-France Region, 75020, France

RECRUITING

University Medical Center Groningen

Groningen, Provincie Groningen, 9713 GZ, Netherlands

NOT YET RECRUITING

Erasmus Medical Center Rotterdam

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

NOT YET RECRUITING

Related Publications (1)

• Ottenbourgs T, van Gorp T, Kridelka F, Baert T, Denys H, Selle F, Baas I, Van Rompuy AS, Lambrechts D, Van Nieuwenhuysen E. A phase II, multicenter, open-label study of abemaciclib and letrozole in patients with estrogen receptor-positive rare ovarian cancer: ALEPRO trial. Int J Gynecol Cancer. 2024 Apr 1;34(4):627-630. doi: 10.1136/ijgc-2023-005189.

  PMID: 38453176 DERIVED

MeSH Terms

Interventions

abemaciclib; Letrozole

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Els Van Nieuwenhuysen, MD PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Els Van Nieuwenhuysen, MD PhD

CONTACT

+3216342531; els.vannieuwenhuysen@uzleuven.be

Tine Ottenbourgs

CONTACT

+3216348131; tine.ottenbourgs@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 24, 2023
• Study Start: November 30, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); NL (3); FR (6)