ALPINE: Maintenance Letrozole/Abemaciclib
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDana-Farber Cancer Institute
About this trial
The purpose of this research study is to see if the study drugs abemaciclib and letrozole are effective and safe for participants with estrogen-receptor positive (ER+), mismatch repair proficient, tumor protein p53 (TP53) wild-type endometrial cancer.
The names of the study drugs involved in this study are:
* Abemaciclib (a type of cyclin-dependent kinase (CDK) inhibitor) * Letrozole (a type of aromatase inhibitor)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must have histologically confirmed either i) endometrioid endometrial cancer or ii) endometrial carcinosarcoma with endometrioid epithelial component.
Participants must have ER-positive disease, defined as ≥ 1 percent of tumor cell nuclei being immunoreactive by immunohistochemistry (IHC). If multiple analyses have been performed, judgment should be based on the most recent biopsy or pathology specimen analyzed in a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory.
Tumor must be TP53 wild-type as determined by immunohistochemistry (IHC) or via CLIA-certified targeted Next-Generation Sequencing (NGS); IHC assessment of p53 status is included in the NCCN guidelines of uterine neoplasms for the molecular analysis of endometrial carcinoma.
Participants must have mismatch repair proficient (MMRP) endometrial cancer as determined by immunohistochemistry (IHC) or polymerase chain reaction (PCR) or any CLIA-certified next generation sequencing assay.
Disqualifiers
Participants who have received previous treatment with CDK4/6 inhibitors, including but not limited to previous abemaciclib therapy.
Any gastrointestinal dysfunctions that could interfere with the absorption of study drugs (e.g., bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea CTCAE v 5.0 > grade 1).
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 starting study treatment.
The patient has active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.
Trial design
Design model
Single group
Treatments tested in this trial
Abemaciclib
DrugCDK inhibitor, tablet taken orally per protocol.
Letrozole
DrugAromatase inhibitor, tablet taken orally per protocol.
Pembrolizumab
DrugHumanized immunoglobulin G4 monoclonal antibody, 4mL (milliliter) single-dose vial, via intravenous (into the vein) infusion per institutional standard of care.
Treatment groups
32 Participants
are divided into 1 treatment groupGroup A: Arm 1: Abemaciclib + LetrozoleExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Median Progression Free Survival (PFS)
PFS is defined as the time from the date the participant was registered to the date of documented progressive disease (PD) by RECIST version 1.1 or death (regardless of cause) in the absence of progression, regardless of whether the participant withdraws from study drug or receives another anti-cancer therapy prior to progression. Participants alive without disease progression are censored at date of last disease evaluation. A participant who dies without progression, and the death is \>12 weeks after the last evaluable tumor assessment, is censored for PFS at the date of last disease evaluation. A participant who has no baseline or no post treatment tumor assessment is censored at 0 days for PFS, unless she dies \< 12 weeks from randomization, in which case the PFS event date is the death date. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum, taking as reference the smallest sum on study with at least 5 mm absolute increase.
Time frame
Up to 2 yearsSecondary outcomes
1
Grade 3-5 Adverse Events (AE) Rate
Grade 3-5 AE rate is defined as the proportion of patients who experience a grade 3-5 adverse event based on the Common Toxicity Criteria for Adverse Events version 5.0 as reported on case report form.
Time frame
Up to 2 years and 1 month2
Median Overall Survival (OS)
OS is defined as the time from registration to death due to any cause, or censored at date last known alive based on Kaplan-Meier methodology.
Time frame
Up to 5 years3
Objective Response Rate (ORR)
The percentage of participants who achieved complete response (CR) and partial response (PR) based on RECIST 1.1 criteria. Complete Response (CR) for target lesion: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \< 10 mm. Partial Response (PR) for target lesion: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame
Up to 2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Dana-Farber Cancer Institute
Lead sponsor
Eli Lilly and Company
Collaborator
Source ClinicalTrials.gov