Abemaciclib for the Treatment of Rb Wild-Type Refractory or Relapsed Extensive Stage Small Cell Lung Cancer
- Subjects must have histologically confirmed extensive stage small cell lung cancer
- Pathology confirmed retinoblastoma (Rb) wild type tested by NGS
- Subjects must have: * Platinum refractory disease: defined as no response after 1-2 cycles of chemotherapy, or * Relapse: defined as initial response but relapse < 90 days after completing platinum-based chemotherapy
- Subjects must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
- Subjects must have biopsy or archival tumor material available for biomarker analyses with confirmed availability of FFPE tumor tissue
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients who received chemotherapy must have recovered (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 chemotherapy dose and enrollment (provided the patient did not receive radiotherapy)
- 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 enrollment
- Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
- The patient is able to swallow oral medications
- 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
- The effects of the study medication on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) throughout study participation and for 6 months after completing treatment
- Subjects must have the ability to understand and the willingness to sign a written informed consent document
- Prior treatment toxicities not resolved to =< grade 1 according to NCI CTCAE version 5.0 (except alopecia, and neuropathy)
- Subjects receiving any other investigational agents
- The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgement of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance < 30 ml/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)
- Females who are pregnant or lactating
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib
- 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
- 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
- Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with abemaciclib. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated
I. To evaluate the efficacy, as measured by overall response rate (ORR), of abemaciclib in patients with wild type retinoblastoma (Rb) chemotherapy-refractory extensive stage small cell lung cancer (ES-SCLC).
I. To evaluate the disease control rate (DCR) at 8 weeks, in patients with wild type Rb chemotherapy refractory ES-SCLC treated with abemaciclib.
II. To estimate progression free survival (PFS) at 6 months and overall survival (OS) at 1 year of wild type Rb, chemotherapy-refractory ES-SCLC patients, treated with abemaciclib.
III. To evaluate the frequency and severity of toxicities per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading (version 5.0), in patients with wild type Rb chemo-refractory ES-SCLC treated with abemaciclib.
IV. To estimate duration of response in all responders (DoR) to abemaciclib in patients with wild type Rb chemotherapy-refractory ES-SCLC.
I. Immunohistochemistry (IHC) to measure Rb, INSMA1, YAP1 and p16 INK4A expression and correlate degree of expression with clinical response.
II. To perform a next generation sequencing (NGS) on pretreatment diagnostic tumor formalin-fixed paraffin-embedded (FFPE) and correlate different genomic biomarkers including MTB and PDL1 to outcome and treatment response.
Patients receive abemaciclib orally (PO) twice daily (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 for 30 days, every 3 months for 2 years, every 6 months for 5 years, and then annually for up to 10 years.
Trial Phase Phase II
Trial Type Treatment
Case Comprehensive Cancer Center
- Primary ID CASE1519
- Secondary IDs NCI-2020-00422
- Clinicaltrials.gov ID NCT04010357