Trial Title:
Abemaciclib and Letrozole in Patients With Estrogen Receptor-positive Rare Ovarian Cancer
NCT ID:
NCT05872204
Condition:
Low Grade Serous Ovarian Carcinoma
Adult Type Granulosa Cell Tumor
Conditions: Official terms:
Granulosa Cell Tumor
Letrozole
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Abemaciclib
Description:
150 mg tablet twice daily
Arm group label:
Abemaciclib and letrozole
Other name:
Verzenios
Intervention type:
Drug
Intervention name:
Letrozole
Description:
2.5 mg tablet once daily
Arm group label:
Abemaciclib and letrozole
Other name:
Femara
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.
Detailed description:
Patients with recurrent, persistent and/or metastatic estrogen receptor-positive rare
ovarian cancer, who failed one line of platinum based chemotherapy for advanced or
recurrent disease, will be included in this study. One cohort will include low-grade
serous or endometrioid epithelial ovarian cancer and another cohort will include adult
type granulosa cell tumors. The results of large randomized phase 3 trials of the
combination of an aromatase inhibitor combined with a CDK4/6 inhibitor in hormone
sensitive, HER2 negative breast cancer can form the basis for a trial with this drug
combination in hormone sensitive rare ovarian cancer. The aim is to increase the response
rate to aromatase inhibitors and the duration of response in this study population with
limited therapeutic options, monitor the quality of life and explore the (epi)genomic
signatures that correlate with response or endocrine resistance. Abemaciclib will be
supplied as capsules administered orally, 150 mg every 12 hours (Q12H) on Days 1 to 28 of
a 28-day cycle, plus letrozole 2.5 mg OD Days 1 to 28 of a 28-day cycle.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntary written informed consent of the participant or their legally authorized
representative has been obtained prior to any screening procedures.
2. 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.
3. Histological confirmation of diagnosis of low-grade serous (original diagnosis of
low-grade serous carcinoma or original diagnosis of serous borderline tumor with
subsequent diagnosis of low-grade serous carcinoma )or low-grade endometrioid
carcinoma of ovary, fallopian tube or peritoneum or granulosa-cell tumor of the
adult type and ER positivity on immunohistochemistry. In order to prevent inclusion
of patients with high-grade serous carcinoma, diagnosis of low-grade serous
carcinoma will be verified as part of screening review by a gynecologic pathologist.
Tissue for confirmation can be from primary tumor or recurrence.
4. 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.
5. Age > 18 years at time of study entry.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
7. 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.
8. 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.
9. Patients who were previously treated with letrozole or another aromatase inhibitor
are allowed, but capped at 10 patients in each cohort.
10. 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.
11. 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.
12. Abnormal organ function is permitted. However, patients must have:
1. absolute neutrophil count ≥1500/mL
2. platelets ≥100.000/mL
3. hemoglobin ≥9 g/dL
4. estimated creatinine clearance ≥ 45 ml/min as calculated using the method
standard for the institution
5. total serum bilirubin ≤1.5 X ULN
6. aspartate aminotransferase (AST/SGOT) and/or alanine aminotransferase
(ALT/SGPT) ≤3 X ULN
7. alkaline phosphatase ≤2.5x ULN (or ≤5.0x ULN if liver or bone metastases)
Exclusion Criteria:
1. 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).
2. 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).
3. 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).
4. 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.
5. Patient cannot have previously received a prior cyclin dependent kinase inhibitor
(CDKi).
6. Known Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection.
7. Inability or unwillingness to swallow pills.
8. 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).
9. Active infection requiring intravenous (IV) antibiotics or antifungals, or other
uncontrolled recurrent illness requiring hospitalization.
10. 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.
11. Prior hematopoietic stem cell or bone marrow transplantation.
12. 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.
13. Known abnormalities in coagulation such as bleeding diathesis, or treatment with
anticoagulants precluding intramuscular injections of goserelin (if applicable).
14. Known or possible hypersensitivity to letrozole or abemaciclib or any of their
excipients.
15. Pre/perimenopausal women with a known hypersensitivity to gnRH
(gonadotropin-releasing hormone) agonists.
16. Patients who are pregnant or breastfeeding.
17. Participation in an interventional Trial with an investigational medicinal product
(IMP) or device. The patient has received an experimental treatment in a clinical
trial within the last 30 days or 5 half-lives, whichever is longer, prior to
randomization, or is currently enrolled in any other type of medical research (for
example: medical device) judged by the sponsor not to be scientifically or medically
compatible with this study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UZ Gent
Address:
City:
Gent
Zip:
9000
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Hannelore Denys, MD PhD
Phone:
+3293322692
Email:
hannelore.denys@uzgent.be
Investigator:
Last name:
Hannelore Denys, MD PhD
Email:
Principal Investigator
Facility:
Name:
UZ Leuven
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Els Van Nieuwenhuysen, MD PhD
Phone:
+3216342531
Email:
els.vannieuwenhuysen@uzleuven.be
Contact backup:
Last name:
Tine Ottenbourgs
Phone:
+3216348131
Email:
tine.ottenbourgs@uzleuven.be
Investigator:
Last name:
Els Van Nieuwenhuysen, MD PhD
Email:
Principal Investigator
Facility:
Name:
CHU de Liège
Address:
City:
Liège
Zip:
4000
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Frédéric Kridelka, MD
Phone:
+3243237169
Email:
Frederic.Kridelka@chuliege.be
Investigator:
Last name:
Frédéric Kridelka, MD
Email:
Principal Investigator
Facility:
Name:
Institut De Cancerologie Strasbourg Europe
Address:
City:
Strasbourg
Zip:
67200
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Lauriane Eberst, MD
Email:
l.eberst@icans.eu
Investigator:
Last name:
Lauriane Eberst, MD
Email:
Principal Investigator
Facility:
Name:
Institut Bergonie
Address:
City:
Bordeaux
Zip:
33000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Coriolan Lebreton, MD
Email:
c.lebreton@bordeaux.unicancer.fr
Investigator:
Last name:
Coriolon Lebreton, MD
Email:
Principal Investigator
Facility:
Name:
Institut Universitaire Du Cancer Toulouse-Oncopole
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Laurence Gladieff, MD
Email:
gladieff.laurence@iuct-oncopole.fr
Investigator:
Last name:
Laurence Gladieff, MD
Email:
Principal Investigator
Facility:
Name:
Institut De Cancerologie De L'Ouest
Address:
City:
Saint-Herblain
Zip:
44800
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Dominique Berton, MD
Email:
Dominique.berton@ico.unicancer.fr
Investigator:
Last name:
Dominique Berton, MD
Email:
Principal Investigator
Facility:
Name:
Centre Leon Berard
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Isabelle Ray-Coquard, MD PhD
Email:
isabelle.ray-coquard@lyon.unicancer.fr
Investigator:
Last name:
Isabelle Ray-Coquard, MD PhD
Email:
Principal Investigator
Facility:
Name:
Groupe Hospitalier Diaconesses Croix Saint Simon
Address:
City:
Paris
Zip:
75020
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Frédéric Selle, MD
Email:
fselle@hopital-dcss.org
Investigator:
Last name:
Frédéric Selle, MD
Email:
Principal Investigator
Facility:
Name:
Erasmus Medical Center Rotterdam
Address:
City:
Rotterdam
Zip:
3015 GD
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Ingrid Boere, MD
Email:
i.boere@erasmusmc.nl
Investigator:
Last name:
Ingrid Boere, MD
Email:
Principal Investigator
Facility:
Name:
University Medical Center Groningen
Address:
City:
Groningen
Zip:
9713 GZ
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Hilde Jalving, MD
Email:
m.jalving@umcg.nl
Investigator:
Last name:
Hilde Jalving, MD
Email:
Principal Investigator
Facility:
Name:
University Medical Center Utrecht
Address:
City:
Utrecht
Zip:
3584 CX
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Inge Baas, MD
Email:
I.O.Baas-3@umcutrecht.nl
Investigator:
Last name:
Inge Baas, MD
Email:
Principal Investigator
Start date:
November 30, 2023
Completion date:
October 2026
Lead sponsor:
Agency:
Universitaire Ziekenhuizen KU Leuven
Agency class:
Other
Collaborator:
Agency:
Kom Op Tegen Kanker
Agency class:
Other
Collaborator:
Agency:
Eli Lilly and Company
Agency class:
Industry
Collaborator:
Agency:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Agency class:
Other
Source:
Universitaire Ziekenhuizen KU Leuven
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05872204
