Endometrial CancerPhase 2NCT06366347
ALPINE: Maintenance Letrozole/Abemaciclib
A Phase 2 study testing Abemaciclib, Letrozole and Pembrolizumab in people with Endometrial Cancer and Recurrent Endometrial Cancer, run by Dana-Farber Cancer Institute at 8 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endometrial Cancer, Recurrent Endometrial Cancer, TP53
- What is being tested?
- Abemaciclib, Letrozole and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 8 sitesUnited States
- Study dates
- 25 Sep 2024to 1 Mar 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 30Show fewer
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Panagiotis Konstantinopoulos, MD, PhD contact
8 sites in 1 country
United States8 sites, 6 recruiting
- Recruiting
University of Colorado Cancer Center
Aurora, Colorado, 80045
Grace Batcha, grace.batcha@cuanschutz.edu
Bradley Corr, MD
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Meghan Shea, MD, 617-667-3723, mshea4@bidmc.harvard.edu
Meghan Shea, MD
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Panagiotis Konstantinopoulos, MD, PhD, 617-632-2334, Panagiotis_Konstantinopoulos@dfci.harvard.edu
Panagiotis Konstantinopoulos, MD, PhD
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Panagiotis Konstantinopoulos, MD, PhD, 617-632-2334, Panagiotis_Konstantinopoulos@dfci.harvard.edu
Panagiotis Konstantinopoulos, MD, PhD
- Withdrawn
Dana-Farber Cancer Institute at Foxborough
Foxborough, Massachusetts, 02035
- Withdrawn
Dana-Farber Cancer Institute at Milford
Milford, Massachusetts, 01757
- Recruiting
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Christine Pappaterra, BSN, RN, OCN, christine-pappaterra@ou.edu
Christina Washington, MD
- Recruiting
Dana-Farber Cancer Institute at South Shore Hospital
Weymouth, Massachusetts, 02190
Meredith Faggen, MD, 781-624-4800, meredith_faggen@dfci.harvard.edu
Meredith Faggen, MD
About this study
Official title: A Phase 2 Trial of Maintenance Abemaciclib/Letrozole After Systemic Therapy in Patients With Advanced or Recurrent Estrogen Receptor Positive, Mismatch Repair Proficient, TP53 Wildtype Endometrial Cancer
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)
Read the detailed description
This is a phase 2, single arm trial of maintenance letrozole/abemaciclib after carboplatin/paclitaxel chemotherapy with or without anti-PD-(L)1 blockade in patients with advanced or recurrent estrogen receptor (ER) positive (ER+), mismatch repair proficient (MMRP), tumor protein p53 (TP53) wild-type endometrial cancer.
The U.S. Food and Drug Administration (FDA) has not approved abemaciclib or letrozole for endometrial cancer but they have been approved for other uses.
The research study procedures include screening for eligibility, study treatment visits, X-rays, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron Emission Tomography (PET) scans, blood tests, and electrocardiograms (EKGs).
Participants will be administered study drugs for up to 2 years and will be followed for 3 years after completing study treatment.
It is expected that about 32 people will take part in this research study.
Eli Lilly is supporting this research study by providing funding and the study drug abemaciclib.
- Conditions
- Endometrial Cancer, Recurrent Endometrial Cancer, TP53
- Being tested
- Abemaciclib, Letrozole, Pembrolizumab
- Keywords
- TP53 wild-type endometrial cancer, Endometrial Cancer, Recurrent endometrial cancer
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbemaciclibDrug
Also called Verzenio, LY2835219, C27H32F2N8
CDK inhibitor, tablet taken orally per protocol.
LetrozoleDrug
Also called Femara, C17H11N5
Aromatase inhibitor, tablet taken orally per protocol.
PembrolizumabDrug
Also called Keytruda, MK-3475, Humanized X PD-1-mAB (monoclonal antibody) (H409A11) IgG4 (immunoglobulin G4), C6504H10004N1716O2036S46
Humanized immunoglobulin G4 monoclonal antibody, 4mL (milliliter) single-dose vial, via intravenous (into the vein) infusion per institutional standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Abemaciclib + Letrozole | Experimental | Participants will be stratified by Primary Stage IVb (4b) vs. Primary Measurable Stage III (3)/IVa (4a) vs. Recurrent Endometrial Cancer and will complete study procedures as follows:
* Baseline visit with X-ray, CT, MRI, or PET scan.
* Cycles 1 through 3:
--Days 1 through 21 of 21 day cycle: Predetermined dose of Abemaciclib 2x per day. Predetermined dose of Letrozole 1x per day.
* Cycle 4 and every 2 cycles thereafter:
--Days 1 through 21 of 21 day cycle: Predetermined dose of Abemaciclib 2x per day. Predetermined dose of Letrozole 1x per day.
* X-ray, CT, MRI, or PET scan every 9 weeks for first 9 months, then every 12 months.
* End of Treatment visit with assessments and X-ray, CT, MRI, or PET scan.
* Follow up for up to 3 years. Receives: Drug: Abemaciclib; Drug: Letrozole; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Secondary outcomes (3)
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.
Measured: Up to 2 years and 1 month
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.
Measured: Up to 5 years
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2024
- Study start25 Sep 2024
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Panagiotis Konstantinopoulos, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Panagiotis Konstantinopoulos, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06366347
- Sponsor's protocol ID
- 23-695
- Status last verified
- Sep 2026
- First submitted
- 8 Apr 2024
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.