Targeted therapy for advanced lung cancer using Abemaciclib
Targeted Therapy With CDK4/6 Inhibitors in Chemo- Refractory/Relapsed, Rb Wild-type Extensive Small Cell Lung Cancer (SCLC), Large Cell Neuroendocrine Lung Cancer, Extrapulmonary Small Cell Cancers and Other High Grade Neuroendocrine Cancers of the Lung, an Open Label Phase 2 Trial.
This study is testing if a new drug called Abemaciclib can help people with advanced small cell lung cancer and other tough-to-treat cancers that didn’t get better with previous chemotherapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 29 (estimated) |
| Ages | 19 Years and up |
| Sex | All |
| Sponsor | Case Comprehensive Cancer Center Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Cleveland, Ohio) |
| Trial ID | NCT04010357 on ClinicalTrials.gov |
What this trial studies
This study evaluates the effectiveness and safety of Abemaciclib, a CDK4/6 inhibitor, in patients with advanced small cell lung cancer and other high-grade neuroendocrine cancers that have not responded to previous chemotherapy. It is a multicenter, non-randomized, phase 2 trial focusing on patients with wild type Rb extensive stage disease. The trial aims to measure the overall response rate and progression-free survival after treatment with Abemaciclib. Participants will be monitored for safety and efficacy over a defined period.
Who should consider this trial
Good fit: Ideal candidates include individuals with extensive stage small cell lung cancer or other high-grade neuroendocrine lung cancers that are platinum refractory or have relapsed after chemotherapy.
Not a fit: Patients with non-small cell lung cancer or those who have not undergone prior chemotherapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new option for patients with refractory lung cancers, potentially improving their outcomes.
How similar studies have performed: Other studies have shown promise with CDK4/6 inhibitors in various cancers, suggesting potential for success in this novel application.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* Subjects must have histologically confirmed extensive stage small cell lung cancer, large cell neuroendocrine lung cancer, extrapulmonary small cell cancer or other high grade neuroendocrine cancer of the lung.
* Pathology confirmed Retinoblastoma wild type tested by NGS or ctDNA.
* Subjects must have:
* Platinum refractory disease: defined as no response after 1-2 cycles of chemotherapy, or
* Relapse: defined as initial response but relapse after completing platinum-based chemotherapy.
* Subjects must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
* Subjects shall have archival tumor material for correlative studies if available. If tissue is not available they still may be eligible for the trial
* Performance status: 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). Please refer to eligibility criteria for specific laboratory requirements.
* 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 CNS-directed therapy shows no evidence of progression.
* The patient is able to swallow oral medications.
* The patient has adequate organ function for all of the following criteria, as defined below:
* Hematologic system:
* absolute neutrophil count (ANC) ≥1.5 × 10\^9/L
* Platelets ≥100 × 10\^9/L
* Hemoglobin ≥8g/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).
* Hepatic system:
* Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times upper limit of normal (ULN) and direct bilirubin within normal limits are permitted.
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × 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.
Exclusion Criteria:
* 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 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).
* Females who are pregnant or lactating.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Abemaciclib.
* Subjects with uncontrolled intercurrent illness including, syncope of cardiac etiology, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, sudden cardiac arrest, or psychiatric illness/social situations that would limit compliance with study requirements.
* 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.
* 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.
Where this trial is running
Cleveland, Ohio
- Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center — Cleveland, Ohio, United States (Recruiting)
Study contacts
- Principal investigator: Afshin Dowlati, MD — Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
- Study coordinator: Afshin Dowlati, MD
- Email: afshin.dowlati@uhhospitals.org
- Phone: +1 216-844-1228
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.