ALEPRO: abemaciclib and letrozole in estrogen receptor positive rare ovarian cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Nov 2023 → ongoing

Decision date (initial)

2023-10-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Eli Lilly · Kom Op Tegen Kanker

External identifiers

EU CT number

2023-503533-21-00

ClinicalTrials.gov

NCT05872204

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To determine the overall response rate (ORR) of the combination of abemaciclib and letrozole according to RECIST 1.1.

Secondary objectives 6

1. To determine the duration of response (DOR) of the combination of abemaciclib and letrozole in intention-to-treat (ITT) population.
2. To assess the nature, frequency and maximum degree of toxicity associated with this combination.
3. To determine the progression-free survival (PFS) of women receiving the combination of letrozole and abemaciclib.
4. To determine the overall survival (OS) of women receiving the combination of letrozole and abemaciclib.
5. To assess the change from baseline in quality of life scores as assessed by EQ-5D-5L and EORTC QLQ-C30 questionnaires.
6. To determine the clinical benefit rate (CBR).

Conditions and MedDRA coding

Low-grade serous ovarian cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
2. For Stage 1: Patients who were previously treated with letrozole or another aromatase inhibitor are allowed, but capped at 10 patients in each cohort. For Stage 2, Cohort 1 (LGSOC): Patients who were previously treated with letrozole or another aromatase inhibitor are allowed. In both stages and cohorts: Patients who showed progression while on letrozole or another aromatase inhibitor during their most recent progression are not eligible to participate.
3. 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 inclusion.
4. 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 or be considered for radiological castration after a negative serum or urine human chorionic gonadotropin (hCG) test.
5. Abnormal organ function is permitted. However, patients must have: i. absolute neutrophil count >/= 1500/mL ii. platelets >/= 100,000/mL iii. hemoglobin >/= 9 g/dL d iv. estimated creatinine clearance >/= 45 ml/min as calculated using the method standard for the institution v. total serum bilirubin </= 1.5 X ULN vi. aspartate aminotransferase (AST/SGOT) and/or alanine aminotransferase (ALT/SGPT) </= 3 X ULN vii. Alkaline phosphatase ≤2.5x ULN (or ≤5.0x ULN if liver or bone metastases)
6. 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, as defined by local pathologist.
7. Patients who have previously received at least one line of platinum-based chemotherapy for advanced or recurrent disease.
8. For Stage 1, Cohort 1 (LGSOC): only patients where platinum is still an option (platinum-free interval (PFI) ≥ 6 months) are eligible with no limitations in prior chemotherapy regimens and a maximum of 2 prior endocrine therapy regimens. Patients where platinum is not an option (PFI < 6 months) and platinum refractory patients are not allowed. For Stage 1, Cohort 2 (AGCT): 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. Five patients where platinum is not an option (PFI < 6 months) are allowed. Platinum refractory patients are not allowed. For Stage 2: 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. Patients where platinum is not an option and platinum refractory patients are not allowed. Ten patients where platinum is not an option are allowed with no limitations in prior chemotherapy regimens and maximum of 2 prior endocrine therapy regimens.
9. Age > 18 years at time of study entry.
10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
11. Patient must have recurrent, evaluable and 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.
12. Pre- and post-treatment tissue biopsy and (ctDNA) blood samples 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.
13. For women with at least one remaining ovary: 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, 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.

Exclusion criteria 18

1. For Stage 1, Cohort 1 (LGSOC): patients where platinum is not an option (PFI < 6 months) and platinum refractory patients are not allowed. For Stage 1, Cohort 2 (AGCT): five patients where platinum is not an option are allowed. For Stage 2: patients with platinum refractory disease are not allowed.
2. Active infection requiring intravenous (IV) antibiotics or antifungals, or other uncontrolled recurrent illness requiring hospitalization.
3. 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.
4. Prior hematopoietic stem cell or bone marrow transplantation.
5. 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.
6. Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of goserelin (if applicable).
7. Known or possible hypersensitivity to letrozole or abemaciclib or any of their excipients.
8. Pre/perimenopausal women with a known hypersensitivity to gnRH (gonadotropin-releasing hormone) agonists.
9. Patients who are pregnant or breastfeeding.
10. 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 inclusion. A washout period of at least 21 days is required between last chemotherapy dose and inclusion (provided the patient did not receive radiotherapy).
11. 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 <45 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).
12. 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).
13. 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.
14. Patient cannot have previously received a prior cyclin dependent kinase inhibitor (CDKi).
15. Known Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection.
16. Inability or unwillingness to swallow pills.
17. 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).
18. 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 inclusion, 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To determine the overall response rate (ORR) of the combination of abemaciclib and letrozole in the study population, as defined by RECIST v1.1.

Secondary endpoints 5

1. Efficacy endpoints: duration of response (DOR), clinical benefit ratio (CBR), progression free survival (PFS), overall survival (OS)
2. Safety endpoints, including but not limited to TEAEs, SAEs, hospitalizations, clinical laboratory tests, vital signs, and physical examinations
3. To evaluate participant-reported symptoms, function and global health status/QOL based on EORTC QLQ-C30 scales
4. To evaluate health status in the study population to inform decision modeling for health economic evaluation using the EQ-5D 5L index score
5. Exploratory endpoints: investigate potential biomarkers related to cyclin pathway and/or the pathogenesis of low-grade serous/endometrioid ovarian cancer and granulosa cell tumors.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Els Van Nieuwenhuysen

Public contact point

Organisation

UZ Leuven

Contact name

Els Van Nieuwenhuysen

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications