Ignite Creation Date:
2024-06-16 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06424067
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-24
First Post:
2024-04-18
Brief Title:
Phase 2 Study of Fingolimod in Lung Cancers
Sponsor:
Medical University of South Carolina
Organization:
Medical University of South Carolina
Study Overview
Official Title:
A Phase II Study of Fingolimod in Patients With Non-Small Cell and Small Cell Lung Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a single-institution open-labeled study using fingolimod FTY720Gilenya in patients with non-small cell lung cancer NSCLC and small cell lung cancer SCLC who have progressed on chemo-immunotherapy The study design will be a 6 patient safety lead-in with 2 cohorts of patients for efficacy analysis where fingolimod 05 mg will be taken orally once daily
Detailed Description:
Lung cancer is the second most common cancer and the leading cause of cancer death in the United States There were approximately 237000 new cases of lung cancer that were diagnosed in 2022 The past decade has seen a revolution of new advances in the management of both non-small cell lung cancer NSCLC and small cell lung cancer SCLC with remarkable progress in screening diagnosis and treatment The advances in systemic treatment have been driven primarily by the development of molecularly targeted therapeutics immune-checkpoint inhibitors and anti-angiogenic agents all of which have transformed this field with significantly improved patient outcomes Despite these advances the prognosis for patients with advanced NSCLC and SCLC is poor particularly after the failure of a platinum-based chemotherapy regimen and check point inhibitors with limited options available for patients Therefore new methods of targeting these malignancies are crucial Fingolimod is a sphingosine analog that has demonstrated strong tumor suppressive activity in preclinical models of lung cancers and warrants further study
This proposed study is a single institution Phase II clinical trial to investigate the safety and efficacy of fingolimod in patients with NSCLC and SCLC Fingolimod is a small molecule derived from myriocin that acts as a sphingosine analog It is currently FDA-approved to treat patients with relapsing forms of multiple sclerosis MS including clinically isolated syndrome relapsing-remitting disease and active secondary progressive disease by binding to sphingosine-1-phosphate S1P receptors 1 3 4 and 5 causing T lymphocyte egression and retention in peripheral lymphoid organs leading to immunosuppression However it can act as an antagonist for the S1P receptor promoting tumor suppression in multiple cancer cell lines and mouse models inhibiting cell proliferation and inducing cancer cell death There are multiple studies demonstrating its activity in preclinical models of lung cancer Fingolimod induces a type of programmed cell death called necroptosis in lung cancer cells This is mediated by activation of the tumor suppressor protein phosphatase 2A PP2A through interaction with the PP2A inhibitor I2PP2A Specifically work done using the adenocarcinoma cell line A549 and small cell carcinoma cell line H1341 showed that fingolimod-mediated stress induced the formation of ceramidosomes leading to plasma membrane blebbing compromised membrane integrity and necroptosis
This study will evaluate the safety tolerability and response rate in patients with NCSLC and SCLC who have progressed on front-line therapy including chemotherapy immune checkpoint inhibitors and targeted agents It will contribute to the development of new methods for targeting these malignancies and provide insights into the potential use of fingolimod as a treatment option for these patients
This proposed study is a single institution Phase II clinical trial to investigate the safety and efficacy of fingolimod in patients with NSCLC and SCLC Fingolimod is a small molecule derived from myriocin that acts as a sphingosine analog It is currently FDA-approved to treat patients with relapsing forms of multiple sclerosis MS including clinically isolated syndrome relapsing-remitting disease and active secondary progressive disease by binding to sphingosine-1-phosphate S1P receptors 1 3 4 and 5 causing T lymphocyte egression and retention in peripheral lymphoid organs leading to immunosuppression However it can act as an antagonist for the S1P receptor promoting tumor suppression in multiple cancer cell lines and mouse models inhibiting cell proliferation and inducing cancer cell death There are multiple studies demonstrating its activity in preclinical models of lung cancer Fingolimod induces a type of programmed cell death called necroptosis in lung cancer cells This is mediated by activation of the tumor suppressor protein phosphatase 2A PP2A through interaction with the PP2A inhibitor I2PP2A Specifically work done using the adenocarcinoma cell line A549 and small cell carcinoma cell line H1341 showed that fingolimod-mediated stress induced the formation of ceramidosomes leading to plasma membrane blebbing compromised membrane integrity and necroptosis
This study will evaluate the safety tolerability and response rate in patients with NCSLC and SCLC who have progressed on front-line therapy including chemotherapy immune checkpoint inhibitors and targeted agents It will contribute to the development of new methods for targeting these malignancies and provide insights into the potential use of fingolimod as a treatment option for these patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None