Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00037817
Status:
COMPLETED
Last Update Posted:
2019-09-30
First Post:
2002-05-21
Brief Title:
Phase I Study of Gene Induction Mediated by Sequential DecitabineDepsipeptide Infusion With or Without Concurrent Celecoxib in Subjects With Pulmonary and Pleural Malignancies
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Study of Gene Induction Mediated by Sequential DecitabineDepsipeptide Infusion With or Without Concurrent Celecoxib in Subjects With Pulmonary and Pleural Malignancies
Status:
COMPLETED
Status Verified Date:
2016-11-30
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:
Background
Previously we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung cancer cells following exposure to the DNA demethylating agent Decitabine DAC We have also demonstrated that DAC mediated target gene expression and apoptosis can be significantly enhanced in cancer cells by subsequent exposure to the histone deacetylase HDAC inhibitor Depsipeptide FK228 DP Furthermore we have demonstrated that following DAC or DACDP exposure cancer cells can be recognized by cytolytic T cells specific for the cancer testis antigen NY-FSO-1
This Phase I study will evaluate gene induction in thoracic oncology patients mediated by sequential DACDP treatment with or without the selective COX-2 inhibitor celecoxib
Objectives
Evaluation of the pharmacokinetics and toxicity of continuous 72-hour intravenous Decitabine DAC infusion followed by 4-hour intravenous infusion of Depsipeptide FK228 DP with or without oral celecoxib in patients with unresectable cancers involving the lungs or pleura
Analysis of NY-ESO-1 p16 and p21 expression in cancer specimens before and after sequential DecitabineDepsipeptide treatment
Analysis of serologic response to NY-ESO-1 before and after sequential drug treatment
Analysis of apoptosis in tumor biopsies before and after sequential DecitabineDepsipeptide treatment
Refinement of laser capture microdissection and micro-array techniques for analysis of gene expression profiles in tumor tissues
Eligibility
Patients with histologically or cytologically proven primary small cell or non-small cell lung cancers advanced esophageal cancers pleural mesotheliomas or non-thoracic cancers with metastases to the lungs or pleura
Patients must be 18 years or older with an ECOG performance status of 0-2 and have adequate pulmonary reserve evidenced by FEV1 and DLCO greater than the 30 predicted and less than 50 mm Hg and p02 greater than 60 mm Hg on room air ABG
Patients must have a platelet count greater than 100000 an ANC equal to or greater than 1500 without transfusion or cytokine support a normal PT and adequate hepatic function as evidenced by a total bilirubin of less than 15 x upper limits of normal Serum creatinine less than or equal to 16 mgml or the creatinine clearance must be greater than 70 mlmin173m2
Design
Patients with inoperable malignancies involving lungs or pleura will receive two cycles of 72-hour intravenous infusion of Decitabine followed by 4-hour Depsipeptide infusion using a Phase I study design
Decitabine will be administered by continuous infusion on days 1-4 and patient cohorts will receive escalating doses of Depsipeptide administered on day 4 and day 10 of a 34 day cycle
Once the MTD and toxicities for sequential DACDP have been identified additional cohorts of 6 lung cancer patients and 6 mesothelioma patients will receive sequential DACDP administered at the MTD as outlined above with celecoxib 400mg bid administered on days 4-34 of each treatment cycle as a means to enhance target cell apoptosis and facilitate anti-tumor immune recognitionresponse
Pharmacokinetics systemic toxicity and response to therapy will be recorded Tumor biopsies will be obtained prior to and after therapy to evaluate expression of NY-ESO-1 tumor antigen as well as p16 and p21 tumor suppressor genes which are known to be modulated by chromatin structure Additional analysis will be undertaken to evaluate the extent of apoptosis in tumor tissues and to determine if immune recognition of NY-ESO-1 can be demonstrated following sequential DACDP - celecoxib treatment
As the exact set of comparisons and analyses to be performed will be determined following completion of the trial and will be based on limited numbers of patients the analyses will be considered exploratory and hypothesis generating rather than definitive
A total of 40 patients will be enrolled
Previously we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung cancer cells following exposure to the DNA demethylating agent Decitabine DAC We have also demonstrated that DAC mediated target gene expression and apoptosis can be significantly enhanced in cancer cells by subsequent exposure to the histone deacetylase HDAC inhibitor Depsipeptide FK228 DP Furthermore we have demonstrated that following DAC or DACDP exposure cancer cells can be recognized by cytolytic T cells specific for the cancer testis antigen NY-FSO-1
This Phase I study will evaluate gene induction in thoracic oncology patients mediated by sequential DACDP treatment with or without the selective COX-2 inhibitor celecoxib
Objectives
Evaluation of the pharmacokinetics and toxicity of continuous 72-hour intravenous Decitabine DAC infusion followed by 4-hour intravenous infusion of Depsipeptide FK228 DP with or without oral celecoxib in patients with unresectable cancers involving the lungs or pleura
Analysis of NY-ESO-1 p16 and p21 expression in cancer specimens before and after sequential DecitabineDepsipeptide treatment
Analysis of serologic response to NY-ESO-1 before and after sequential drug treatment
Analysis of apoptosis in tumor biopsies before and after sequential DecitabineDepsipeptide treatment
Refinement of laser capture microdissection and micro-array techniques for analysis of gene expression profiles in tumor tissues
Eligibility
Patients with histologically or cytologically proven primary small cell or non-small cell lung cancers advanced esophageal cancers pleural mesotheliomas or non-thoracic cancers with metastases to the lungs or pleura
Patients must be 18 years or older with an ECOG performance status of 0-2 and have adequate pulmonary reserve evidenced by FEV1 and DLCO greater than the 30 predicted and less than 50 mm Hg and p02 greater than 60 mm Hg on room air ABG
Patients must have a platelet count greater than 100000 an ANC equal to or greater than 1500 without transfusion or cytokine support a normal PT and adequate hepatic function as evidenced by a total bilirubin of less than 15 x upper limits of normal Serum creatinine less than or equal to 16 mgml or the creatinine clearance must be greater than 70 mlmin173m2
Design
Patients with inoperable malignancies involving lungs or pleura will receive two cycles of 72-hour intravenous infusion of Decitabine followed by 4-hour Depsipeptide infusion using a Phase I study design
Decitabine will be administered by continuous infusion on days 1-4 and patient cohorts will receive escalating doses of Depsipeptide administered on day 4 and day 10 of a 34 day cycle
Once the MTD and toxicities for sequential DACDP have been identified additional cohorts of 6 lung cancer patients and 6 mesothelioma patients will receive sequential DACDP administered at the MTD as outlined above with celecoxib 400mg bid administered on days 4-34 of each treatment cycle as a means to enhance target cell apoptosis and facilitate anti-tumor immune recognitionresponse
Pharmacokinetics systemic toxicity and response to therapy will be recorded Tumor biopsies will be obtained prior to and after therapy to evaluate expression of NY-ESO-1 tumor antigen as well as p16 and p21 tumor suppressor genes which are known to be modulated by chromatin structure Additional analysis will be undertaken to evaluate the extent of apoptosis in tumor tissues and to determine if immune recognition of NY-ESO-1 can be demonstrated following sequential DACDP - celecoxib treatment
As the exact set of comparisons and analyses to be performed will be determined following completion of the trial and will be based on limited numbers of patients the analyses will be considered exploratory and hypothesis generating rather than definitive
A total of 40 patients will be enrolled
Detailed Description:
Background
Previously we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung cancer cells following exposure to the DNA demethylating agent Decitabine DAC We have also demonstrated that DAC mediated target gene expression and apoptosis can be significantly enhanced in cancer cells by subsequent exposure to the histone deacetylase HDAC inhibitor Depsipeptide FK228 DP Furthermore we have demonstrated that following DAC or DACDP exposure cancer cells can be recognized by cytolytic T cells specific for the cancer testis antigen NY-FSO-1
This Phase I study will evaluate gene induction in thoracic oncology patients mediated by sequential DACDP treatment with or without the selective COX-2 inhibitor celecoxib
Objectives
Evaluation of the pharmacokinetics and toxicity of continuous 72-hour intravenous Decitabine DAC infusion followed by 4-hour intravenous infusion of Depsipeptide FK228 DP with or without oral celecoxib in patients with unresectable cancers involving the lungs or pleura
Analysis of NY-ESO-1 p16 and p21 expression in cancer specimens before and after sequential DecitabineDepsipeptide treatment
Analysis of serologic response to NY-ESO-1 before and after sequential drug treatment
Analysis of apoptosis in tumor biopsies before and after sequential DecitabineDepsipeptide treatment
Refinement of laser capture microdissection and micro-array techniques for analysis of gene expression profiles in tumor tissues
Eligibility
Patients with histologically or cytologically proven primary small cell or non-small cell lung cancers advanced esophageal cancers pleural mesotheliomas or non-thoracic cancers with metastases to the lungs or pleura
Patients must be 18 years or older with an ECOG performance status of 0-2 and have adequate pulmonary reserve evidenced by FEV1 and DLCO greater than the 30 predicted and less than 50 mm Hg and p02 greater than 60 mm Hg on room air ABG
Patients must have a platelet count greater than 100000 an ANC equal to or greater than 1500 without transfusion or cytokine support a normal PT and adequate hepatic function as evidenced by a total bilirubin of less than 15 x upper limits of normal Serum creatinine less than or equal to 16 mgml or the creatinine clearance must be greater than 70 mlmin173m2
Design
Patients with inoperable malignancies involving lungs or pleura will receive two cycles of 72-hour intravenous infusion of Decitabine followed by 4-hour Depsipeptide infusion using a Phase I study design
Decitabine will be administered by continuous infusion on days 1-4 and patient cohorts will receive escalating doses of Depsipeptide administered on day 4 and day 10 of a 34 day cycle
Once the MTD and toxicities for sequential DACDP have been identified additional cohorts of 6 lung cancer patients and 6 mesothelioma patients will receive sequential DACDP administered at the MTD as outlined above with celecoxib 400mg bid administered on days 4-34 of each treatment cycle as a means to enhance target cell apoptosis and facilitate anti-tumor immune recognitionresponse
Pharmacokinetics systemic toxicity and response to therapy will be recorded Tumor biopsies will be obtained prior to and after therapy to evaluate expression of NY-ESO-1 tumor antigen as well as p16 and p21 tumor suppressor genes which are known to be modulated by chromatin structure Additional analysis will be undertaken to evaluate the extent of apoptosis in tumor tissues and to determine if immune recognition of NY-ESO-1 can be demonstrated following sequential DACDP - celecoxib treatment
As the exact set of comparisons and analyses to be performed will be determined following completion of the trial and will be based on limited numbers of patients the analyses will be considered exploratory and hypothesis generating rather than definitive
A total of 40 patients will be enrolled
Previously we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung cancer cells following exposure to the DNA demethylating agent Decitabine DAC We have also demonstrated that DAC mediated target gene expression and apoptosis can be significantly enhanced in cancer cells by subsequent exposure to the histone deacetylase HDAC inhibitor Depsipeptide FK228 DP Furthermore we have demonstrated that following DAC or DACDP exposure cancer cells can be recognized by cytolytic T cells specific for the cancer testis antigen NY-FSO-1
This Phase I study will evaluate gene induction in thoracic oncology patients mediated by sequential DACDP treatment with or without the selective COX-2 inhibitor celecoxib
Objectives
Evaluation of the pharmacokinetics and toxicity of continuous 72-hour intravenous Decitabine DAC infusion followed by 4-hour intravenous infusion of Depsipeptide FK228 DP with or without oral celecoxib in patients with unresectable cancers involving the lungs or pleura
Analysis of NY-ESO-1 p16 and p21 expression in cancer specimens before and after sequential DecitabineDepsipeptide treatment
Analysis of serologic response to NY-ESO-1 before and after sequential drug treatment
Analysis of apoptosis in tumor biopsies before and after sequential DecitabineDepsipeptide treatment
Refinement of laser capture microdissection and micro-array techniques for analysis of gene expression profiles in tumor tissues
Eligibility
Patients with histologically or cytologically proven primary small cell or non-small cell lung cancers advanced esophageal cancers pleural mesotheliomas or non-thoracic cancers with metastases to the lungs or pleura
Patients must be 18 years or older with an ECOG performance status of 0-2 and have adequate pulmonary reserve evidenced by FEV1 and DLCO greater than the 30 predicted and less than 50 mm Hg and p02 greater than 60 mm Hg on room air ABG
Patients must have a platelet count greater than 100000 an ANC equal to or greater than 1500 without transfusion or cytokine support a normal PT and adequate hepatic function as evidenced by a total bilirubin of less than 15 x upper limits of normal Serum creatinine less than or equal to 16 mgml or the creatinine clearance must be greater than 70 mlmin173m2
Design
Patients with inoperable malignancies involving lungs or pleura will receive two cycles of 72-hour intravenous infusion of Decitabine followed by 4-hour Depsipeptide infusion using a Phase I study design
Decitabine will be administered by continuous infusion on days 1-4 and patient cohorts will receive escalating doses of Depsipeptide administered on day 4 and day 10 of a 34 day cycle
Once the MTD and toxicities for sequential DACDP have been identified additional cohorts of 6 lung cancer patients and 6 mesothelioma patients will receive sequential DACDP administered at the MTD as outlined above with celecoxib 400mg bid administered on days 4-34 of each treatment cycle as a means to enhance target cell apoptosis and facilitate anti-tumor immune recognitionresponse
Pharmacokinetics systemic toxicity and response to therapy will be recorded Tumor biopsies will be obtained prior to and after therapy to evaluate expression of NY-ESO-1 tumor antigen as well as p16 and p21 tumor suppressor genes which are known to be modulated by chromatin structure Additional analysis will be undertaken to evaluate the extent of apoptosis in tumor tissues and to determine if immune recognition of NY-ESO-1 can be demonstrated following sequential DACDP - celecoxib treatment
As the exact set of comparisons and analyses to be performed will be determined following completion of the trial and will be based on limited numbers of patients the analyses will be considered exploratory and hypothesis generating rather than definitive
A total of 40 patients will be enrolled
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-C-0205 | None | None | None |