Fulvestrant and Abemaciclib in Treating Patients with Stage III- IV Low Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
- Patients with clinical or surgical stage III or IV low-grade serous ovarian, primary peritoneal, or fallopian tube carcinomas who in the judgement of the treating physician are unlikely to achieve optimal surgical cytoreduction and have been recommended to receive neoadjuvant therapy.
- Histological diagnosis must be based on surgical or core biopsy not just fine needle aspiration. Biopsies performed at other institutions must undergo pathology review and confirmation at MD Anderson Cancer Center.
- Tissue from an archival tissue sample or fresh tissue obtained from a core or excisional biopsy of a tumor lesion.
- Willingness to provide pre- and post-treatment tissue for translational studies. Pre-treatment fresh frozen tissue must be available for research purposes. This tissue can be collected from preoperative laparoscopy, other diagnostic biopsy, or a research-specific biopsy.
- Signed informed consent on protocol LAB02-188.
- Patients whose clinical biopsies are found to be insufficient for the planned translational studies must be willing to undergo a research biopsy.
- Patients must have measurable disease by RECIST v1.1. a. Measurable disease is defined at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each target lesion must be > 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or > 10 mm when measured by spiral CT.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- Absolute neutrophil count >= 1500/mL.
- Platelets >= 100,000/mL.
- Hemoglobin >= 9 g/dL.
- Estimated creatinine clearance >= 60 ml/min as calculated using the method standard for the institution.
- Total serum bilirubin =< 1.5 X upper limit of normal (ULN).
- Aspartate aminotransferase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 X ULN (=< 5 X ULN in patients with bone or liver metastases).
- Serum creatinine =< 1.5 x ULN.
- Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE 5.0 grade =< 1 except for residual alopecia or grade 2 peripheral neuropathy prior to first dose of study treatment. A washout period of at least 21 days is required between last chemotherapy dose and first dose of study treatment (provided the patient did not receive radiotherapy).
- Patients who received adjuvant 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 first dose of study treatment.
- Women of child-bearing potential (intact uterus) MUST have a negative serum or urine human chorionic gonadotropin (HCG) test within 72 hours prior to receiving the first dose of study medication. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Women of childbearing potential should be willing to use 2 methods of birth control, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Pre/perimenopausal women must be amenable to be treated with goserelin. All patients will be rendered post-menopausal secondary to concomitant administration of goserelin.
- Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures.
- Patients who are pregnant or breastfeeding.
- 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).
- Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval.
- Diagnosis of another malignancy within 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
- Previous chemotherapy or hormonal therapy for treatment of ovarian cancer.
- Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
- Inability or unwillingness to swallow pills.
- Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization.
- Inability to comply with the study and follow-up procedures.
- History of any of the following: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), sudden cardiac arrest.
- Prior hematopoietic stem cell or bone marrow transplantation.
- Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if applicable).
- Known or possible hypersensitivity to fulvestrant, or abemaciclib or any of their excipients.
- Pre/perimenopausal women with a known hypersensitivity to gonadotrophin releasing hormone (gnRH) agonists.
I. To estimate the clinical benefit rate (partial response [PR], complete response [CR], and stable disease) associated with neoadjuvant abemaciclib plus fulvestrant in patients with untreated, advanced low grade serous carcinoma (LGSC) who are not candidates for upfront cytoreductive surgery based upon assessed response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
I. To describe tumor transcriptional and proteomic expression changes induced by neoadjuvant abemaciclib + fulvestrant in patients with LGSC.
II. To determine expression of estrogen receptor (ER) and progesterone receptor (PR), and proliferative index (ki67) and their correlation with clinical benefit.
III. To determine the nature, frequency, and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 for the combination.
Patients receive fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1 and day 1 of cycles 2-4, and abemaciclib orally (PO) twice daily (BID) on days 1-28. Pre- or perimenopausal patients also receive goserelin acetate subcutaneously (SC) every 12 weeks. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery. Beginning 3-6 weeks after surgery, patients receive fulvestrant IM on day 1 and abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
Trial Phase Phase II
Trial Type Treatment
M D Anderson Cancer Center
Amir Anthony Jazaeri
- Primary ID 2017-0405
- Secondary IDs NCI-2018-00941
- Clinicaltrials.gov ID NCT03531645