ACTIVE_NOT_RECRUITING

Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC

Conditions

Small-cell Lung Cancer Large Cell Neuroendocrine Carcinoma of the Lung Extrapulmonary Small Cell Carcinoma Platinum refractory disease Wild Type Rb Extensive Stage SCLC High grade neuroendocrine cancers of the lung

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to: * Test how well the study medicine Abemaciclib, a CDK4/6 inhibitor, works to shrink lung cancer tumors in the body. * Test the safety of Abemaciclib when given to participants with small cell lung cancer (SCLC), large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung. Specifically, this study is looking at SCLC, large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung that have not responded to treatment (refractory) or come back after treatment with chemotherapy (relapsed) as the study medication has been shown to be effective any time the disease relapses not just in the first few months.

Official Title

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.

Quick Facts

Study Start:2020-01-13

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04010357

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:19 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Principal Investigator

Afshin Dowlati, MD

PRINCIPAL_INVESTIGATOR

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study Locations (Sites)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065

United States

Collaborators and Investigators

Sponsor: Case Comprehensive Cancer Center

Afshin Dowlati, MD, PRINCIPAL_INVESTIGATOR, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-01-13

Study Completion Date2025-12

Study Record Updates

Study Start Date2020-01-13

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

Platinum refractory disease
Wild Type Rb Extensive Stage SCLC
High grade neuroendocrine cancers of the lung

Additional Relevant MeSH Terms

Small-cell Lung Cancer
Large Cell Neuroendocrine Carcinoma of the Lung
Extrapulmonary Small Cell Carcinoma