Abemaciclib and Letrozole to Treat Endometrial Cancer

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.