Breast Cancer
Conditions
Keywords
Breast Cancer
Brief summary
The drug being studied is Trastuzumab, a medicine that is used to slow or stop the growth of cancerous tumors that are HER-2 positive. Patients are being asked to participate in this study because they have been diagnosed with having tumor cells in their spinal fluid. This study will investigate the safety and effects of this drug when given directly into the spinal fluid. Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Breast Cancer The purpose of this research study is to determine a safe dose of the drug Trastuzumab and then determine how effective this treatment is.
Detailed description
Phase I: Patients will be treated in cohorts of 3-6 based on standard phase I dose escalation parameters requiring 0/3 or 1/6 patients per cohort to have a DLT before dose escalation. Dosing is as follows: Cohort 1-10 mg IT, cohort 2-20 mg IT, cohort 3-30 mg IT and cohort 4-40 mg IT. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks. Toxicity for DLT will be assessed during first 4 weeks of treatment. Phase II: Patients will be treated with the MTD or maximal defined dose. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks.
Interventions
RADIATIONTrastuzumab
Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks
Sponsors
Northwestern University
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ELIGIBILITY CRITERIA * HER2 positive (IHC 3+ and/or FISH positive) breast cancer patients with leptomeningeal metastases by MRI or CSF (if MRI is negative). o Review will be performed for cases not reviewed at Northwestern for confirmation, but will not preclude patients from entering the trial (pathology report is sufficient for registration). * Patients can have concomitant brain metastases as long as they do not require active treatment or have been treated. * Patients with leptomeningeal disease from ependymomas, gliomas, and medulloblastoma will be eligible for phase I * Life expectancy \> 8 weeks * Normal renal (creatinine \< 1.5 ULN), liver (bilirubin \< 1.5 x ULN, transaminases \< 3.0 x ULN, except in known hepatic metastasis, wherein may be \< 5 x ULN) and blood counts (WBC \> 3.0, Neutrophils \> 1500, platelets \>100 000, Hemoglobin \> 10). * LVEF \> 50% * KPS \> 50 * Age \> 18 years * Cannot be on systemic agents (chemotherapy) that have CNS penetration unless they develop leptomeningeal metastases while on these agent(s) and have controlled systemic disease. May continue on IV trastuzumab, lapatinib or hormonal agents if controlling systemic disease and developed LM while on therapy. Patients requiring systemic chemotherapy are eligible but will not be able to start treatment until after the first assessment by imaging and cytology. * Patients may need a CSF flow study at the discretion of the treating principal investigator. If a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment. Concurrent radiation is not allowed. * Patients should be \> 2 weeks from RT treatment and all effects of treatment should have resolved * No limit on prior systemic or IT therapies. * CSF sampling to document LM if not documented on MRI. * Must be willing to have an Ommaya reservoir placed. * NO history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for the disease for a minimum of 3 years. * Significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol. * Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study. * Women may not be pregnant or breast-feeding. * Ability to sign an informed consent; can be signed by family member or health care proxy. Informed consent must be done prior to registration on study. * All patients must have given signed, informed consent prior to registration on study. * No known hypersensitivity to trial medications Note: The eligibility criteria listed above are interpreted literally and cannot be waived.
Exclusion criteria
\- Any deviations from the inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | From treatment initiation through the first 4 weeks of treatment. | Patients will be treated using a standard 3+3 dose-escalation design for cohorts 1 and 2. This will be followed by an accelerated phase I for cohorts 3 and 4, and then a standard 3 + 3 for the 5th cohort. In the accelerated phase (cohorts 3 and 4), 1 patient will be enrolled per cohort; if a toxicity is seen in that patient then the cohort would be expanded to 6 patients to allow for 1/6 patients per cohort to have a dose limiting toxicity (DLT) before dose escalation. Cohort 5 will enroll a total of 6 patients regardless of the toxicity experienced in patient one. However, if 2 or more DLTs are observed in cohort 5, cohort 4 will be reopened to enroll of a total of 6 patients. Whatever dose is ultimately declared the MTD should have 6 patients total. If 1/6 DLTs are seen in cohort 5 that will be considered the MTD. Dosing is as follows: Cohort 1-10 mg IT Cohort 2-20 mg IT Cohort 3-40 mg IT Cohort 4-60 mg IT Cohort 5-80 mg IT |
| Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Baseline then at 4 weeks, 8 weeks and then every 8 weeks +/- 3 days, until disease progression or toxicity,range of cycles completed 1-22 cycles where 1 cycle = 28 days. | Best response will be assessed using a combination CSF cytology assessment, radiographic assessment and clinical function assessments. Best response will be defined as the best response seen during treatment as compared to baseline that is confirmed on subsequent response assessment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Define the CSF PK of IT Trastuzumab. | CSF analysis for cytology will be done every 2 weeks when CSF is obtained for PK and then every 4 weeks | Patients may need a CSF flow study at the discretion of the treating principal investigator. If a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment. Concurrent radiation is not allowed. |
Countries
United States
Participant flow
Recruitment details
The study opened for accrual on April 26, 2011 with first patient being treated August 1, 2011, with an accrual goal of up to 48 patients for phase I/II combined. Amendment 5 added 5th cohort to allow higher dose. The study was suspended April 12, 2014 and reopened on August 28, 2014 for phase II. The study closed to accrual June 2, 2016.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - Trastuzumab 10mg IT 2/Week Intrathecal Trastuzumab 10 mg IT will be administered in Cohort 1 of dose escalation.
Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.
1 cycle = 28 days. | 3 |
| Cohort 2 - Trastuzumab 20mg IT 2/Week Intrathecal Trastuzumab 20 mg IT will be administered in Cohort 2 of dose escalation.
Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.
1 cycle = 28 days. | 3 |
| Cohort 3- Trastuzumab 40mg IT 2/Week Intrathecal Trastuzumab 40 mg IT will be administered in Cohort 3 of dose escalation.
Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.
1 cycle = 28 days. | 1 |
| Cohort 4 - Trastuzumab 60mg IT 2/Week Intrathecal Trastuzumab 60 mg IT will be administered in Cohort 4 of dose escalation.
Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.
1 cycle = 28 days. | 1 |
| Cohort 5 - 80mg IT 2/Week Intrathecal Trastuzumab 80 mg IT will be administered in Cohort 5 of dose escalation.
Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.
1 cycle = 28 days. | 7 |
| Phase II - Transtuzumab 80mg IT 2/Week Intrathecal Trastuzumab 10 mg IT will be administered in phase II portion of the study.
Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.
1 cycle = 28 days. | 19 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Completed 4 Weeks/1 Cycle of Treatment | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 |
| Completed 8 Weeks/2 Cycles of Treatment | Progressive Disease | 1 | 1 | 0 | 0 | 2 | 5 |
| Follow-up Every 3 Months Until Death | Follow-up Considered Complete | 0 | 0 | 0 | 0 | 1 | 0 |
| Follow-up Every 3 Months Until Death | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Started 9th Week/Cycle 3 of Treatment | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Started 9th Week/Cycle 3 of Treatment | Progressive disease | 1 | 1 | 1 | 1 | 0 | 4 |
| Started 9th Week/Cycle 3 of Treatment | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 2 - Trastuzumab 20mg IT 2/Week | Cohort 3- Trastuzumab 40mg IT 2/Week | Cohort 4 - Trastuzumab 60mg IT 2/Week | Cohort 1 - Trastuzumab 10mg IT 2/Week | Cohort 5 - 80mg IT 2/Week | Phase II - Transtuzumab 80mg IT 2/Week |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 6 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 7 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 29 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 34 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Female | 32 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 3 / 3 | 1 / 1 | 1 / 1 | 5 / 7 | 17 / 19 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 1 / 1 | 1 / 1 | 7 / 7 | 19 / 19 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 1 / 1 | 1 / 1 | 3 / 7 | 13 / 19 |
Outcome results
Primary
Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Best response will be assessed using a combination CSF cytology assessment, radiographic assessment and clinical function assessments. Best response will be defined as the best response seen during treatment as compared to baseline that is confirmed on subsequent response assessment.
Time frame: Baseline then at 4 weeks, 8 weeks and then every 8 weeks +/- 3 days, until disease progression or toxicity,range of cycles completed 1-22 cycles where 1 cycle = 28 days.
Population: All patients were assessed for response. Patients unable to be assessed were determined to have progressive disease and counted. Cohort results for this outcome measure were analysed combined and at the MTD of 80mg IT (Cohort 5 + phase II). The objective was to determine preliminary response data for this treatment combination.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Complete Response | 0 Participants |
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Partial Response | 6 Participants |
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Stable Disease | 18 Participants |
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Progressive Disease | 10 Participants |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Progressive Disease | 8 Participants |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Complete Response | 0 Participants |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Stable Disease | 13 Participants |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | Partial Response | 5 Participants |
Primary
Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Patients will be treated using a standard 3+3 dose-escalation design for cohorts 1 and 2. This will be followed by an accelerated phase I for cohorts 3 and 4, and then a standard 3 + 3 for the 5th cohort. In the accelerated phase (cohorts 3 and 4), 1 patient will be enrolled per cohort; if a toxicity is seen in that patient then the cohort would be expanded to 6 patients to allow for 1/6 patients per cohort to have a dose limiting toxicity (DLT) before dose escalation. Cohort 5 will enroll a total of 6 patients regardless of the toxicity experienced in patient one. However, if 2 or more DLTs are observed in cohort 5, cohort 4 will be reopened to enroll of a total of 6 patients. Whatever dose is ultimately declared the MTD should have 6 patients total. If 1/6 DLTs are seen in cohort 5 that will be considered the MTD. Dosing is as follows: Cohort 1-10 mg IT Cohort 2-20 mg IT Cohort 3-40 mg IT Cohort 4-60 mg IT Cohort 5-80 mg IT
Time frame: From treatment initiation through the first 4 weeks of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 0 DLTs |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 0 DLTs |
| Cohort 3- Trastuzumab 40mg IT 2/Week | Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 0 DLTs |
| Cohort 4 - Trastuzumab 60mg IT 2/Week | Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 0 DLTs |
| Cohort 5 - 80mg IT 2/Week | Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 1 DLTs |
Other Pre-specified
Define the CSF PK of IT Trastuzumab.
Patients may need a CSF flow study at the discretion of the treating principal investigator. If a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment. Concurrent radiation is not allowed.
Time frame: CSF analysis for cytology will be done every 2 weeks when CSF is obtained for PK and then every 4 weeks
Post Hoc
Median Overall Survival (OS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Overall Survival (OS) will be measured from start of treatment until death from any cause. To estimate OS, Kaplan-Meier curves will be calculated and median OS will be determined from the progression-free survival curve.
Time frame: From start of treatment until death from any cause for up to 60 months.
Population: Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on OS of patients with this drug combination
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Median Overall Survival (OS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 8.738 percentage of patients |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Median Overall Survival (OS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 8.328 percentage of patients |
Post Hoc
Median Progression Free Survival (PFS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Progression Free Survival (PFS) will be measured from the time of treatment initiation until the first documentation of progression. To estimate PFS, Kaplan-Meier curves will be calculated and the median PFS will be determined from the progression-free survival curve. Progression will be defined as worsening clinical signs or development of new clinical symptoms that the Investigator feels can be attributed to Leptomeningeal disease.
Time frame: From start of treatment, and during treatment until progressive disease for up to 30 months.
Population: Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on PFS of patients with this drug combination
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Median Progression Free Survival (PFS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 1.885 Months |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Median Progression Free Survival (PFS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | 2.148 Months |
Post Hoc
Overall Survival (OS) at 6 and 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Overall Survival (OS) will be measured from the time of treatment initiation until death from any cause. To estimate OS probability at 6 and 12 months, Kaplan-Meier curves will be calculated and OS at 612 months will be determined from the overall survival curve.
Time frame: At 6 and 12 months from start of treatment
Population: Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on OS of patients with this drug combination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Overall Survival (OS) at 6 and 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | OS at 6 months | 0.562 Probability of Survival |
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Overall Survival (OS) at 6 and 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | OS at 12 months | 0.406 Probability of Survival |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Overall Survival (OS) at 6 and 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | OS at 12 months | 0.458 Probability of Survival |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Overall Survival (OS) at 6 and 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | OS at 6 months | 0.542 Probability of Survival |
Post Hoc
Progression Free Survival (PRS) at 6 Months and at 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Progression Free Survival (PFS) will be measured from the time of treatment initiation until the first documentation of progression. To estimate the probability of PFS at 6 months and 12 months, Kaplan-Meier curves will be calculated and PFS at 6 months and 12 months will be determined from the progression-free survival curve. Progression will be defined as worsening clinical signs or development of new clinical symptoms that the Investigator feels can be attributed to Leptomeningeal disease.
Time frame: At 6 and 12 months from start of treatment
Population: Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on PFS of patients with this drug combination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Progression Free Survival (PRS) at 6 Months and at 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | PFS at 6 months | 0.235 Probability of Survival |
| Cohort 1 - Trastuzumab 10mg IT 2/Week | Progression Free Survival (PRS) at 6 Months and at 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | PFS at 12 months | 0.118 Probability of Survival |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Progression Free Survival (PRS) at 6 Months and at 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | PFS at 6 months | 0.269 Probability of Survival |
| Cohort 2 - Trastuzumab 20mg IT 2/Week | Progression Free Survival (PRS) at 6 Months and at 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. | PFS at 12 months | 0.115 Probability of Survival |