Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a phase II single arm trial to determine the percentage of patients without evidence
of disease progression on abemaciclib and letrozole in advanced stage, persistent or
recurrent endometrioid endometrial cancer at 6 months. Treatment will continue until either
unacceptable toxicity, progression of disease, or investigator/patient request for
withdrawal.
Phase
Phase 2
Funding Agency/Sponsor
Industrial
Disease
Gynecologic Cancer
Enrollment Eligibility
Inclusion Criteria:
1. Patient must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent
endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy.
Histologic confirmation of recurrent disease is required. For cases of persistent
disease, histologic confirmation of the primary disease with radiologic evidence of
progression is required.
2. Patients must have endometrioid histology (all grades allowed) based on hysterectomy
or biopsy specimen (Hormone receptor status is not required for enrollment).
Sites are required to report results of previous MMR, MSI, and ER/PR status testing in
Medidata Rave if available.
3. All patients must have measurable disease. Measurable disease is defined by RECIST
version 1.1. Measurable disease is defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded). Each
lesion must be greater than or equal to 10mm when measured by CT, MRI or caliper
measurement by clinical exam; or greater than or equal to 20mm when measured by chest
x-ray. Lymph nodes must be greater than or equal to 15mm in short axis when measured
by CT or MRI.
Patient must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be
designated as "non-target" lesions unless progression is documented or a biopsy is
obtained to confirm persistence at least 90 days following completion of radiation
therapy.
4. Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. Prior
chemoradiotherapy for a pelvic recurrence is permitted.
Note: Chemotherapy in the setting of Stage IV disease is permitted but the patient
must be without evidence of disease at the completion of chemotherapy and have at
least six months of progression-free survival since the completion of chemotherapy
before detection of the recurrent cancer for which she is receiving treatment on this
protocol.
Prior immunotherapy and/or targeted therapy is allowed in addition to, in combination
with, in lieu of, or subsequent to prior chemotherapy.
Regardless of circumstances, no more than one prior chemotherapy regimen (including
chemo-radiotherapy) is permitted, and no more than one additional systemic therapy is
permitted. Hence, eligible patient may have received 0, 1, or 2 prior lines of
systemic therapy and for women who received two prior lines of therapy, only one of
them may have included chemotherapy.
Patients who received prior chemotherapy, immunotherapy or targeted therapy 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 enrollment. A washout period of at least 21 days is required
between last systemic therapy dose and initiation of therapy.
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 initiation of therapy.
5. Patient must be able to swallow oral medications.
6. Patient must have an ECOG performance status of 0 to 1.
7. Patients must have adequate organ and marrow function as defined below NOTE:
Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower
limit of normal = LLN
Bone marrow function:
- Absolute neutrophil count (ANC) greater than or equal to 1500/mcl
- Platelets greater than or equal to 100,000 cells/mcl
- Hemoglobin greater than or equal to 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
erythrocyte transfusion).
Renal function:
• Creatinine less than or equal to 1.5 x ULN
Hepatic function:
- Bilirubin less than or equal to 1.5 x ULN (Patients with Gilbert's syndrome with
a total bilirubin ≤2 times ULN and direct bilirubin within normal limits are
permitted).
- ALT (alanine aminotransferase) and AST (aspartate aminotransferase) less than or
equal to 3 x ULN
- Alkaline phosphatase less than or equal to 2.5 x ULN
- Albumin greater than or equal to 2.8 g/dL
8. Patients must have signed an approved informed consent and authorization permitting
release of personal health information.
9. Patients must be at least 18 years of age.
10. Patients of childbearing potential must have a negative serum pregnancy test prior to
the study entry and be practicing a highly effective form of contraception during the
study treatment and for 8 weeks after stopping the treatment.
Highly effective contraception methods include combination of any of the following (NOTE:
Estrogen containing contraceptives are prohibited):
- Use of oral, injected, or implanted hormonal methods of contraception or;
- Placement of an intrauterine device (IUD) or intrauterine system (IUS);
- Barrier methods of contraception: condom or occlusive cap (diaphgram or cervical/vault
caps) with spermicidal foam/gel/film/cream/vaginal suppository;
- Total abstinence or;
- Male/female sterilization. Women are considered post-menopausal and not of
child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea
with an appropriate clinical profile (e.g., age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy)
or tubal ligation at least six weeks prior to randomization. In the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow up hormone level assessment is she considered not of child-bearing
potential.
Exclusion criteria
1. Patients who have previously received any CDK4/6 inhibitor.
2. Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers,
or uterine sarcomas.
3. Known intolerance or hypersensitivity to abemaciclib or letrozole.
4. Patients who have previously received hormonal therapy for endometrial cancer.
5. Patients with concomitant invasive malignancy or a history of other invasive
malignancies, with the exception of non-melanoma skin cancer, are excluded if there is
any evidence of other malignancy being present within the past five years. Patients
are also excluded if their previous cancer treatment contraindicates this protocol.
6. Patients receiving chronic treatment with systemic steroids or another
immunosuppressive agent.
7. Patients with 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.
8. Patients with a serious pre-existing 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 (i.e. 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 pre-existing
chronic condition resulting in baseline grade 2 or higher diarrhea).
9. Patients with a known history of cardiac disease. This includes:
- Uncontrolled hypertension, defined as systolic greater than 150mm Hg or diastolic
greater than 90mm Hg despite antihypertensive medications
- Myocardial infarction or unstable angina within 6 months prior to registration.
- New York Heart Association (NYHA) Class II or greater congestive heart failure.
- History of serious ventricular arrhythmia (i.e. ventricular tachycardia or
ventricular fibrillation) or serious cardiac arrhythmia requiring medication,
syncope of cardiovascular etiology or sudden cardiac arrest. This does not
include asymptomatic atrial fibrillation with controlled ventricular rate.
- Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6
months prior to the first date of study therapy.
10. Patients who are pregnant or breast-feeding.
11. Patients with known central nervous system metastases.
12. Patients with known human immunodeficiency virus (HIV) infection.
13. Patients with an impairment of gastrointestinal function or gastrointestinal disease
that may significantly alter the absorption of abemaciclib (i.e. ulcerative disease;
uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome; clinical signs
and symptoms of gastrointestinal obstruction; and/or patients who require parenteral
hydration and/or nutrition).
14. Patients who plan to receive live attenuated vaccines within 1 week of start of
abemaciclib and during the study. Patients should also avoid close contact with others
who have received live attenuated vaccines. Examples of live attenuated vaccines
include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
varicella, and TY21a typhoid vaccines.
15. Patients with active bleeding or pathologic conditions that carry high risk of
bleeding such as known bleeding disorder or coagulopathy.
16. Patients with history of unprovoked venous thrombosis unless taking anticoagulation
treatment for duration of trial.
17. Patients who are currently part of or have participated in any clinical investigation
with an investigational drug within 30 days prior to dosing.