Ignite Creation Date:
2024-05-05 @ 5:07 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00397501
Status:
WITHDRAWN
Last Update Posted:
2017-04-21
First Post:
2006-11-08
Brief Title:
BBBD Followed By Methotrexate and Carboplatin With or Without Trastuzumab in Treating Women With Breast Cancer That Has Spread to the Brain
Sponsor:
OHSU Knight Cancer Institute
Organization:
OHSU Knight Cancer Institute
Study Overview
Official Title:
A Phase III Pilot Study of Patients With Brain Metastasis Secondary to Breast Cancer Treated With Methotrexate and Carboplatin in Conjunction With Blood-Brain Barrier Disruption With Concurrent Trastuzumab in HER-2 Positive Patients
Status:
WITHDRAWN
Status Verified Date:
2017-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
after original approval IRB closed enrollment major revisions required to re-open
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Osmotic blood-brain barrier disruption uses certain drugs such as mannitol to open the blood vessels around the brain and allow tumor-killing substances to be carried directly to the brain Drugs used in chemotherapy such as methotrexate and carboplatin work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Monoclonal antibodies such as trastuzumab can block tumor growth in different ways Some block the ability of tumor cells to grow and spread Others find tumor cells and help kill them or carry tumor-killing substances to them Trastuzumab may also help methotrexate and carboplatin work better by making tumor cells more sensitive to the drugs Giving osmotic blood-brain barrier disruption together with methotrexate carboplatin and trastuzumab may kill more tumor cells
PURPOSE This phase III trial is studying the side effects and best dose of carboplatin when given together with methotrexate and trastuzumab after mannitol in treating women with breast cancer that has spread to the brain
PURPOSE This phase III trial is studying the side effects and best dose of carboplatin when given together with methotrexate and trastuzumab after mannitol in treating women with breast cancer that has spread to the brain
Detailed Description:
OBJECTIVES
Primary
Determine the safety and toxicity associated with blood-brain barrier disruption comprising transfemoral mannitol followed by methotrexate and carboplatin with or without trastuzumab Herceptin in women with brain metastasis secondary to breast cancer Phase I
Determine if overall survival exceeds 5 months in patients with Human Epidermal growth factor Receptor 2HER2-positive or HER2-negative disease treated with this regimen Phase II
Secondary
Determine the overall survival of these patients
Compare the event-free and overall survival steroid use response rates and time to best response in patients with HER2-positive vs HER2-negative disease
Assess the quality of life of patients treated with this regimen
Assess the neuropsychological effects of this treatment regimen in these patients
Determine cerebrospinal fluid levels of trastuzumab before and after blood-brain barrier disruption
OUTLINE This is a multicenter phase I pilot dose-finding study of carboplatin followed by a phase II open-label study
Phase I Patients undergo osmotic blood-brain barrier disruption BBBD comprising mannitol by transfemoral catheterization followed by methotrexate intra-arterially IA over 10 minutes and carboplatin IA over 10 minutes on days 1 and 2 Patients also receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after each dose of carboplatin leucovorin calcium IV or orally every 6 hours on days 3-9 and pegfilgrastim subcutaneously SC on day 4 or filgrastim G-CSF SC beginning on day 4 and continuing until blood counts recover 7-10 days Patients with HER-2 positive disease receive trastuzumab Herceptin IV over 90 minutes within 48 hours prior to BBBD and then weekly for 3 weeks between BBBD therapy sessions Treatment repeats every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive decreasing doses of carboplatin andor methotrexate if the proposed dose is not well tolerated Dose-limiting toxicity is defined as grade IV hematologic toxicity with delay in subsequent treatment courses for 4 weeks OR grade IIIIV nonhematologic toxicity without recovery in 14 days during the course of treatment
Phase II Patients undergo BBBD as in phase I and receive carboplatin and methotrexate at the doses determined in phase I Patients also receive sodium thiosulfate leucovorin calcium and pegfilgrastim or G-CSF as in phase I Patients with HER2-positive disease also receive trastuzumab as in phase I
Neuropsychological assessment is performed at baseline every 6 months during treatment every 6 months for 1 year and then annually thereafter Quality of life is assessed at baseline every 3 months during treatment at the completion of study treatment every 6 months for 1 year and then annually thereafter
After completion of study therapy patients are followed periodically
PROJECTED ACCRUAL A total of 78 patients will be accrued for this study
Primary
Determine the safety and toxicity associated with blood-brain barrier disruption comprising transfemoral mannitol followed by methotrexate and carboplatin with or without trastuzumab Herceptin in women with brain metastasis secondary to breast cancer Phase I
Determine if overall survival exceeds 5 months in patients with Human Epidermal growth factor Receptor 2HER2-positive or HER2-negative disease treated with this regimen Phase II
Secondary
Determine the overall survival of these patients
Compare the event-free and overall survival steroid use response rates and time to best response in patients with HER2-positive vs HER2-negative disease
Assess the quality of life of patients treated with this regimen
Assess the neuropsychological effects of this treatment regimen in these patients
Determine cerebrospinal fluid levels of trastuzumab before and after blood-brain barrier disruption
OUTLINE This is a multicenter phase I pilot dose-finding study of carboplatin followed by a phase II open-label study
Phase I Patients undergo osmotic blood-brain barrier disruption BBBD comprising mannitol by transfemoral catheterization followed by methotrexate intra-arterially IA over 10 minutes and carboplatin IA over 10 minutes on days 1 and 2 Patients also receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after each dose of carboplatin leucovorin calcium IV or orally every 6 hours on days 3-9 and pegfilgrastim subcutaneously SC on day 4 or filgrastim G-CSF SC beginning on day 4 and continuing until blood counts recover 7-10 days Patients with HER-2 positive disease receive trastuzumab Herceptin IV over 90 minutes within 48 hours prior to BBBD and then weekly for 3 weeks between BBBD therapy sessions Treatment repeats every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive decreasing doses of carboplatin andor methotrexate if the proposed dose is not well tolerated Dose-limiting toxicity is defined as grade IV hematologic toxicity with delay in subsequent treatment courses for 4 weeks OR grade IIIIV nonhematologic toxicity without recovery in 14 days during the course of treatment
Phase II Patients undergo BBBD as in phase I and receive carboplatin and methotrexate at the doses determined in phase I Patients also receive sodium thiosulfate leucovorin calcium and pegfilgrastim or G-CSF as in phase I Patients with HER2-positive disease also receive trastuzumab as in phase I
Neuropsychological assessment is performed at baseline every 6 months during treatment every 6 months for 1 year and then annually thereafter Quality of life is assessed at baseline every 3 months during treatment at the completion of study treatment every 6 months for 1 year and then annually thereafter
After completion of study therapy patients are followed periodically
PROJECTED ACCRUAL A total of 78 patients will be accrued for this study
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 |
|---|---|---|---|
| OHSU-2188 | OTHER | OHSU IRB | None |
| SOL-06015 | OTHER | None | None |
| 2188 | OTHER | None | None |