Abemaciclib for the Treatment of Recurrent Ovarian or Endometrial Cancer

Inclusion Criteria

• Histologically-confirmed ovarian epithelial (including fallopian tube and primary peritoneal) cancer or endometrial cancer
• Molecular tumor board confirms that patient’s archival ovarian cancer tumor specimen has been assessed using standard of care genomic profiling and demonstrates CDK4/6 activation features and lack of CCNE amplification or RB deletion
• Molecular tumor board confirms that patient’s archival ovarian cancer tumor specimen demonstrates histological features of low grade serous ovarian cancer (genomic profiling not required for low grade serous ovarian cancer [LGSOC])
• Molecular tumor board confirms that patient’s archival endometrial cancer tumor specimen has positive hormone receptor expression
• 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 enrollment
• 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 study initiation. Radiation therapy that is given for palliative purposes, e.g. for pain control or prevention of a tumor associated complication is allowed during the study. However, study medication should be held during the duration of the radiation therapy and the radiated tumor lesion cannot be used for assessment of treatment response
• The patient is able to swallow oral medications
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Informed consent must be obtained in writing for all patients prior to performing study/screening procedures and prior to registration into the study
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelets >= 100 x 10^9/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
• Total bilirubin =< 1.5 x upper limit of normal (ULN). Patients with Gilbert’s syndrome with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal limits are permitted
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
• Female participants of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a highly effective contraception method during the treatment period and for 3 weeks following the last dose of abemaciclib

Exclusion Criteria

• Anticipation of immediate need for a major surgical procedure (e.g., impending bowel obstruction, gastrointestinal perforation) or radiation therapy during the trial * Radiation therapy that is given for palliative purposes, e.g. for pain control or prevention of a tumor associated complication is allowed during the study * A washout period of 14 days is required between end of major surgery and enrollment
• Diagnosis of any advanced second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, early stage carcinoma of the cervix uteri or breast or any other likely curatively treated early stage malignancy
• The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study
• Any of the following within 6 months prior to trial registration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism
• Unstable brain metastases or carcinomatous meningitis
• Patient of child-bearing potential is evidently pregnant or is breast feeding. A woman with child bearing potential is defined as not surgically sterile or being post-menopausal for less than 6 months
• Patient of child-bearing potential is not willing to use adequate contraceptive precautions. Adequate effective method of contraception are those which result in low failure rates, less than 1% per year, such as non-hormonal intrauterine device (IUD), condoms, sexual abstinence or vasectomized partner
• The patient has serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, 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)
• The patient has active 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
• The patient has a 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
• Current use or anticipated need for: Food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, tilithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delaviridine)
• Other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the patient’s safety, inhibit protocol participation, or interfere with interpretation of trial results, and in the judgment of the investigator would make the patient inappropriate for entry into this trial