ALPINE: Letrozole/Abemaciclib for Endometrial Cancer
This study, called ALPINE, is testing if a combination of two drugs, abemaciclib and letrozole, can help people with certain types of advanced or recurrent endometrial cancer. Abemaciclib is a CDK inhibitor and letrozole is an aromatase inhibitor. The study is looking for people whose cancer is estrogen-receptor positive (ER+), mismatch repair proficient, and has a normal TP53 gene. The main goal is to see how long people live without their cancer growing or spreading (Progression Free Survival), measured for up to 2 years. About 32 people are expected to join this study. The current recruitment status is unclear.
- Study design
- This is a Phase 2 study, meaning it's an early-stage trial to see if the treatment works and is safe. It's a single-arm trial, so all participants will receive the same treatment. About 32 people are expected to participate.
- What's involved
- You would undergo screening, receive study treatment for up to 2 years, and have various tests like X-rays, CT scans, MRIs, PET scans, blood tests, and EKGs. You will be followed for 3 years after treatment ends.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for 3 years after completing study treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06366347
ALPINE: Maintenance Letrozole/Abemaciclib
Recruiting
PHASE2Ages 18+InterventionalTreatmentDana-Farber Cancer InstituteInvestigator-initiated
~32 participants
Updated 2026-02-11 on ClinicalTrials.gov
What's tested:AbemaciclibLetrozolePembrolizumab
At a glance
Recruiting sites
4 of 6 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Median Progression Free Survival (PFS)
Measured over Up to 2 years
Conditions
Where it's being run
6 sites across 1 statesMassachusetts6
Study leadership
- Panagiotis Konstantinopoulos, MD, PhD · PRINCIPAL_INVESTIGATOR · Dana-Farber Cancer Institute
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
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.
No known tumor mutational burden ≥ 10 mutations/megabase (Mb).
No known RB1 mutations or two-copy RB1 deletion.
Participants must have just completed a minimum of 4 cycles and a maximum of 10 cycles of a combination of carboplatin and taxane or a combination of taxane and anti-PD-(L)1 inhibitor therapy (e.g., pembrolizumab, or dostarlimab, or durvalumab).
Participants must have had measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.
Participants are permitted to have received:
a. Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy \[with or without cisplatin\])
b. Prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/paraaortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy. All radiation therapy must have been completed at least 4 weeks prior to registration.
c. Prior hormonal therapy for treatment of endometrial cancer.
Must be able to initiate study drug between 3 to 8 weeks (or 21 to 56 days) after completion of their final dose of chemotherapy and anti-PD-(L)1 blockade (if they were receiving anti-PD-(L)1 blockade).
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix A)
Age ≥ 18 years
Participants must have normal organ and bone marrow function within 2 weeks before starting protocol therapy as defined below:
System Laboratory Value
Hematologic
ANC ≥1.5 × 109 /L
Platelets ≥100 × 109 /L
Hemoglobin ≥8 g/dL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
Hepatic
Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
ALT and AST ≤3 × ULN
Creatinine ≤ 1.5 × institutional ULN, OR
Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above 1.5 x institutional ULN.
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ULN = upper limit of normal.
Ability to understand and the willingness to sign a written informed consent document.
Ability to swallow and retain oral medication.
Participants must be willing to release archival tissue if available. Please see section 9.1.2 and the laboratory manual for tissue requirements.
Exclusion
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.
Major injuries or surgery within 14 days prior to start of study treatment and/or planned major surgery during the on-treatment study period. 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 starting study treatment.
Other malignant disease with disease-free ≤ 3 years except: curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, or ductal carcinoma in situ (DCIS) of the breast or any other cancer deemed by the investigator to be at low risk for recurrence of that malignancy.
Active brain metastases (e.g., stable for \< 8 weeks, no adequate previous treatment with radiotherapy and/or surgery, symptomatic, requiring treatment with anti-convulsant therapy. Corticoid therapy is allowed if administered as stable dose for at least 1 month before starting study treatment).
Females who are pregnant or lactating. The effects of the study agents on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of study agent. Contraceptive methods may include an intrauterine device (IUD) or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. A negative serum pregnancy test is required for study entry from women of childbearing potential.
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/pneumonitis, 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).
Participants who at the time of study enrollment are known to require concomitant therapy with strong CYP3A4 inducers, or strong inhibitors of CYP3A4. Due to potential drug interactions, concomitant use of these medications is not permitted for the duration of treatment on trial. Participants are eligible for study entry if an appropriate substitution is made prior to the first dose of study medication.
Participants with 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.
Individuals with a history of a different malignancy are ineligible with the following exceptions: individuals who have been treated and are disease-free for a minimum of 3 years prior to study enrollment, or individuals who are deemed by the treating investigator to be at low risk for disease recurrence.
What this trial measures
- Median Progression Free Survival (PFS)Up to 2 years
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.