Ignite Creation Date:
2024-05-05 @ 11:04 PM
Last Modification Date:
2024-10-26 @ 10:27 AM
Study NCT ID:
NCT01240590
Status:
COMPLETED
Last Update Posted:
2017-04-10
First Post:
2010-11-11
Brief Title:
A Phase III Trial of Crolibulin EPC2407 Plus Cisplatin in Adults With Solid Tumors With a Focus on Anaplastic Thyroid Cancer ATC
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Trial of Crolibulin EPC2407 Plus Cisplatin in Adults With Solid Tumors With a Focus on Anaplastic Thyroid Cancer ATC
Status:
COMPLETED
Status Verified Date:
2017-02
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
Anaplastic thyroid cancer ATC is one of the most aggressive of all solid tumors chemotherapy and surgery have had no impact on local control or survival of patients with a median survival of 3-7 months
Crolibulin EPC2407 is a microtubulin inhibitor that has been shown to have direct antitumor effects in vivo and in vitro destabilizing spindles and inducing apoptosis resulting in the disruption of neovascular endothelial cells with disruption of blood flow to the tumor Early clinical studies with combretastatin from which crolibulin is derived demonstrated efficacy in a subset of patients with ATC
Objectives
The primary objective in the Phase I portion is to assess the safety and tolerability of cisplatin and crolibulin given in a 21-day cycle in dose-seeking cohorts
We will assess the toxicities of crolibulin coadministered with cisplatin evaluate dose-limiting toxicities DLTs and determine the maximum tolerated dose MTD for the combination
The primary objective in the Phase II portion is to compare the combination crolibulin plus cisplatin versus cisplatin alone in adults with ATC by assessing the duration of progression-free survival PFS comparison of the response rates as evaluated by Response Evaluation Criteria in Solid Tumors RECIST will be an important secondary objective
We plan on biochemical and immunohistochemical analysis of several tumor parameters including mitotic index expression of several proteins including epidermal growth factor receptor EGFR vascular endothelial growth factor receptor VEGFR BRAF excision repair cross-complementation group 1 ERCC1 and tumor protein p53 TP53 Where sufficient tissue is available we will also perform gene expression analysis micro ribonucleic acid microRNA array analysis and compare these with 3-deoxy-3 -18F fluorothymidine FLT-positron emission tomography PET and tumor growth rate constant
Eligibility
Phase I adults age 18 and older with unresectable recurrent or metastatic solid tumors
Phase II adults age 18 and older with anaplastic thyroid cancer
In the phase II portion disease must be evaluable by RECIST
All patients must have adequate hepatic renal and bone marrow function
Design
The Phase I component consists of dose-escalation cohorts of three to six patients in which all patients receive both the study drug crolibulin with cisplatin The MTD and DLT will be determined based on toxicities during the first three weeks of combined therapy
The Phase II component will be a randomization study to either crolibulin with cisplatin or cisplatin monotherapy Patients randomized to cisplatin alone will have the opportunity the opportunity to cross over to the crolibulin arm in the event of tumor progression
Drug administration will take place on days 1 2 and 3 for crolibulin and on day 1 for cisplatin on a 21-day cycle
Maximum number of patients for planned enrollment is 70 During the Phase I portion of the study dose-seeking cohorts of three to six patients will be enrolled until MTD DLT is reached for a maximum of three dose cohorts up to 24 patients if one assumes an expansion cohort to twelve patients at the recommended phase 2 RP2 dose During the randomized Phase II trial comparing the activity of the combination of crolibulin plus cisplatin with cisplatin alone it is estimated that a maximum of 40 patients will be enrolled 11 randomization 20 20 40 patients and we will allow for 6 extra patients to be enrolled to compensate for a small number of non-evaluable patients
Anaplastic thyroid cancer ATC is one of the most aggressive of all solid tumors chemotherapy and surgery have had no impact on local control or survival of patients with a median survival of 3-7 months
Crolibulin EPC2407 is a microtubulin inhibitor that has been shown to have direct antitumor effects in vivo and in vitro destabilizing spindles and inducing apoptosis resulting in the disruption of neovascular endothelial cells with disruption of blood flow to the tumor Early clinical studies with combretastatin from which crolibulin is derived demonstrated efficacy in a subset of patients with ATC
Objectives
The primary objective in the Phase I portion is to assess the safety and tolerability of cisplatin and crolibulin given in a 21-day cycle in dose-seeking cohorts
We will assess the toxicities of crolibulin coadministered with cisplatin evaluate dose-limiting toxicities DLTs and determine the maximum tolerated dose MTD for the combination
The primary objective in the Phase II portion is to compare the combination crolibulin plus cisplatin versus cisplatin alone in adults with ATC by assessing the duration of progression-free survival PFS comparison of the response rates as evaluated by Response Evaluation Criteria in Solid Tumors RECIST will be an important secondary objective
We plan on biochemical and immunohistochemical analysis of several tumor parameters including mitotic index expression of several proteins including epidermal growth factor receptor EGFR vascular endothelial growth factor receptor VEGFR BRAF excision repair cross-complementation group 1 ERCC1 and tumor protein p53 TP53 Where sufficient tissue is available we will also perform gene expression analysis micro ribonucleic acid microRNA array analysis and compare these with 3-deoxy-3 -18F fluorothymidine FLT-positron emission tomography PET and tumor growth rate constant
Eligibility
Phase I adults age 18 and older with unresectable recurrent or metastatic solid tumors
Phase II adults age 18 and older with anaplastic thyroid cancer
In the phase II portion disease must be evaluable by RECIST
All patients must have adequate hepatic renal and bone marrow function
Design
The Phase I component consists of dose-escalation cohorts of three to six patients in which all patients receive both the study drug crolibulin with cisplatin The MTD and DLT will be determined based on toxicities during the first three weeks of combined therapy
The Phase II component will be a randomization study to either crolibulin with cisplatin or cisplatin monotherapy Patients randomized to cisplatin alone will have the opportunity the opportunity to cross over to the crolibulin arm in the event of tumor progression
Drug administration will take place on days 1 2 and 3 for crolibulin and on day 1 for cisplatin on a 21-day cycle
Maximum number of patients for planned enrollment is 70 During the Phase I portion of the study dose-seeking cohorts of three to six patients will be enrolled until MTD DLT is reached for a maximum of three dose cohorts up to 24 patients if one assumes an expansion cohort to twelve patients at the recommended phase 2 RP2 dose During the randomized Phase II trial comparing the activity of the combination of crolibulin plus cisplatin with cisplatin alone it is estimated that a maximum of 40 patients will be enrolled 11 randomization 20 20 40 patients and we will allow for 6 extra patients to be enrolled to compensate for a small number of non-evaluable patients
Detailed Description:
Background
Anaplastic thyroid cancer ATC is one of the most aggressive of all solid tumors chemotherapy and surgery have had no impact on local control or survival of patients with a median survival of 3-7 months
Crolibulin EPC2407 is a microtubulin inhibitor that has been shown to have direct antitumor effects in vivo and in vitro destabilizing spindles and inducing apoptosis resulting in the disruption of neovascular endothelial cells with disruption of blood flow to the tumor
Objectives
The primary objective in the Phase I portion is to assess the safety and tolerability of cisplatin and crolibulin given in a 21-day cycle in dose-seeking cohorts
We will assess the toxicities of crolibulin coadministered with cisplatin evaluate dose-limiting toxicities DLTs and determine the maximum tolerated dose MTD for the combination
The primary objective in the Phase II portion is to compare the combination crolibulin plus cisplatin versus cisplatin alone in adults with ATC by assessing the duration of progression-free survival PFS comparison of the response rates as evaluated by Response Evaluation Criteria in Solid Tumors RECIST will be an important secondary objective
We plan on biochemical and immunohistochemical analysis of several tumor parameters including mitotic index expression of several proteins including epidermal growth factor receptor EGFR vascular endothelial growth factor receptor VEGFR BRAF ERCC1 and tumor protein p53 TP53 Where sufficient tissue is available we will also perform gene expression analysis microRNA array analysis and compare these with 3-deoxy-3-18F fluorothymidine FLT-positron emission tomography PET and tumor growth rate constant
Eligibility
Phase I adults age 18 and older with unresectable recurrent or metastatic solid tumors
Phase II adults age 18 and older with anaplastic thyroid cancer
In the phase II portion disease must be evaluable by RECIST
All patients must have adequate hepatic renal and bone marrow function
Design
The Phase I component consists of dose-escalation cohorts of three to six patients in which all patients receive both the study drug crolibulin with cisplatin The MTD and DLT will be determined based on toxicities during the first three weeks of combined therapy After a minimum of four cycles of concurrent cisplatin and crolibulin if the patient is achieving clinical benefit in the opinion of the investigator but can no longer tolerate cisplatin the patient may receive crolibulin alone until he or she experiences unacceptable toxicity or progressive disease
The Phase II component will be a randomization study to either crolibulin with cisplatin or cisplatin monotherapy Patients randomized to cisplatin alone will have the opportunity to cross over to the crolibulin arm in the event of tumor progression After a minimum of four cycles of concurrent cisplatin and crolibulin if the patient is achieving clinical benefit in the opinion of the investigator but can no longer tolerate cisplatin the patient may receive crolibulin alone until he or she experiences unacceptable toxicity or progressive disease
Drug administration will take place on days 1 2 and 3 for crolibulin and on day 1 for cisplatin on a 21-day cycle
Maximum number of patients for planned enrollment is 70 During the Phase I portion of the study dose-seeking cohorts of three to six patients will be enrolled until MTD DLT is reached for a maximum of three dose cohorts up to 24 patients if one assumes an expansion cohort to twelve patients at the recommended phase 2 RP2 dose During the randomized Phase II trial comparing the activity of the combination of crolibulin plus cisplatin with cisplatin alone it is estimated that a maximum of 40 patients will be enrolled 11 randomization 20 20 40 patients and we will allow for 6 extra patients to be enrolled to compensate for a small number of non-evaluable patients
Anaplastic thyroid cancer ATC is one of the most aggressive of all solid tumors chemotherapy and surgery have had no impact on local control or survival of patients with a median survival of 3-7 months
Crolibulin EPC2407 is a microtubulin inhibitor that has been shown to have direct antitumor effects in vivo and in vitro destabilizing spindles and inducing apoptosis resulting in the disruption of neovascular endothelial cells with disruption of blood flow to the tumor
Objectives
The primary objective in the Phase I portion is to assess the safety and tolerability of cisplatin and crolibulin given in a 21-day cycle in dose-seeking cohorts
We will assess the toxicities of crolibulin coadministered with cisplatin evaluate dose-limiting toxicities DLTs and determine the maximum tolerated dose MTD for the combination
The primary objective in the Phase II portion is to compare the combination crolibulin plus cisplatin versus cisplatin alone in adults with ATC by assessing the duration of progression-free survival PFS comparison of the response rates as evaluated by Response Evaluation Criteria in Solid Tumors RECIST will be an important secondary objective
We plan on biochemical and immunohistochemical analysis of several tumor parameters including mitotic index expression of several proteins including epidermal growth factor receptor EGFR vascular endothelial growth factor receptor VEGFR BRAF ERCC1 and tumor protein p53 TP53 Where sufficient tissue is available we will also perform gene expression analysis microRNA array analysis and compare these with 3-deoxy-3-18F fluorothymidine FLT-positron emission tomography PET and tumor growth rate constant
Eligibility
Phase I adults age 18 and older with unresectable recurrent or metastatic solid tumors
Phase II adults age 18 and older with anaplastic thyroid cancer
In the phase II portion disease must be evaluable by RECIST
All patients must have adequate hepatic renal and bone marrow function
Design
The Phase I component consists of dose-escalation cohorts of three to six patients in which all patients receive both the study drug crolibulin with cisplatin The MTD and DLT will be determined based on toxicities during the first three weeks of combined therapy After a minimum of four cycles of concurrent cisplatin and crolibulin if the patient is achieving clinical benefit in the opinion of the investigator but can no longer tolerate cisplatin the patient may receive crolibulin alone until he or she experiences unacceptable toxicity or progressive disease
The Phase II component will be a randomization study to either crolibulin with cisplatin or cisplatin monotherapy Patients randomized to cisplatin alone will have the opportunity to cross over to the crolibulin arm in the event of tumor progression After a minimum of four cycles of concurrent cisplatin and crolibulin if the patient is achieving clinical benefit in the opinion of the investigator but can no longer tolerate cisplatin the patient may receive crolibulin alone until he or she experiences unacceptable toxicity or progressive disease
Drug administration will take place on days 1 2 and 3 for crolibulin and on day 1 for cisplatin on a 21-day cycle
Maximum number of patients for planned enrollment is 70 During the Phase I portion of the study dose-seeking cohorts of three to six patients will be enrolled until MTD DLT is reached for a maximum of three dose cohorts up to 24 patients if one assumes an expansion cohort to twelve patients at the recommended phase 2 RP2 dose During the randomized Phase II trial comparing the activity of the combination of crolibulin plus cisplatin with cisplatin alone it is estimated that a maximum of 40 patients will be enrolled 11 randomization 20 20 40 patients and we will allow for 6 extra patients to be enrolled to compensate for a small number of non-evaluable 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?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 11-C-0027 | None | None | None |