Recruitment

Recruitment Status
Terminated
Estimated Enrollment
45

Inclusion Criterias

Left-ventricular-ejection fraction (LVEF) of ≥50% by an echocardiogram (ECHO) or by a multiple-gated acquisition (MUGA)
Serum potassium ≥ the institutional LLN
Adequate coagulation parameters.
...
Left-ventricular-ejection fraction (LVEF) of ≥50% by an echocardiogram (ECHO) or by a multiple-gated acquisition (MUGA)
Serum potassium ≥ the institutional LLN
Adequate coagulation parameters.
Ability to swallow oral medications.
Patients with brain metastases previously treated with WBRT/partial brain radiation only must have at least one intracranial tumor lesion ≥ 5mm and must have evidence of intracranial progressive disease
Patients with brain metastases previously untreated with any intracranial radiation (i.e., no whole brain radiation therapy [WBRT]/partial brain radiation or stereotactic radiosurgery [SRS]) must have at least one intracranial tumor lesion that is ≥ 5mm.
Patients who have received WBRT/partial brain radiation for intra-cranial metastases are eligible if treatment was completed ≥28 days prior to the first dose of study drug.
Patient must be discontinued from hormonal therapy a minimum of 1 day prior to the first dose of study treatment.
Patients must be neurologically stable, and if receiving steroids, must be on stable or decreasing doses of corticosteroids and/or anticonvulsants for defined as being on stable low doses of corticosteroids ≥ 5 days prior to the first dose of study treatment.
Immunohistochemical (IHC) score 3+ or
Willingness and ability to comply with trial and follow-up procedures.
Patients with HER2-positive MBC and unequivocal evidence of brain metastases.
Life expectancy ≥12 weeks.
Male patients willing to use adequate contraceptive measures.
Patients must have recovered (>2 week recovery is mandated) from any acute neurosurgical intervention for metastatic CNS disease (e.g., resection, shunt placement) and must be clinically stable. These patients must have residual measurable CNS lesion(s) following the surgical procedure if this site is to serve as the target lesion.
Ability to understand the nature of this trial and give written informed consent.
Serum magnesium ≥ the institutional lower limit of normal (LLN)
Patients previously treated with WBRT/partial brain radiation and SRS must have at least one intracranial tumor lesion ≥ 5mm that was not treated with SRS and must have intracranial disease.
IHC score 1-2+ and confirmed as FISH (Fluorescence in situ hybridization) positive (based on ASCO-CAP guidelines 2013) or
Patients receiving palliative radiation to bone, soft tissue or any other disease sites must have completed this ≥1 week prior to the first dose of study treatment.
Patients with brain metastases previously untreated with any intra-cranial radiation (i.e. no whole brain radiation therapy [WBRT]/partial brain radiation or stereotactic radiosurgery [SRS]) must have at least one intra-cranial tumor lesion that is ≥ 5mm.
Patients previously treated with SRS must either demonstrate disease progression ≥ 12 weeks after completing SRS with a lesion measuring ≥ 5mm or must have at least one intracranial tumor lesion ≥ 5mm that was not treated with SRS.
Patient must have completed biologic therapy ≥3 weeks or 5-half lives whichever is shorter.
Patient must have received prior treatment with HER2-directed therapy such as trastuzumab, either in the adjuvant or metastatic setting.
Patients without prior chemotherapy for MBC are eligible provided the patients relapsed during adjuvant therapy with trastuzumab or ≤6 months following completion of adjuvant therapy. Otherwise, there is no specific minimum or maximum number of previous chemotherapy regimens for MBC.
Prior treatment with lapatinib in the (neo)adjuvant and metastatic setting.
Estrogen receptor (ER) and progesterone receptor (PR) status in the primary or most recent tumor assessment must be known or pending at the time of study registration. Patient's ER/PR status (i.e., positive or negative) does not influence enrollment but is a requirement.
Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of treatment.
Adequate hematologic, renal, and hepatic function.
FISH or ISH (in situ hybridization) positive (based on ASCO-CAP guidelines 2013)
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2.

Exclusion Criterias

Peripheral neuropathy ≥Grade 2 (CTCAE v4.0).
Concurrent treatment with radiation therapy, hormonal therapy, biologic therapy or chemotherapy is not allowed. Low dose corticosteroids (≤30 mg/day prednisone or its equivalent) are allowed.
QTc > 480 ms on screening ECG (using the Fredericia formula)
...
Peripheral neuropathy ≥Grade 2 (CTCAE v4.0).
Concurrent treatment with radiation therapy, hormonal therapy, biologic therapy or chemotherapy is not allowed. Low dose corticosteroids (≤30 mg/day prednisone or its equivalent) are allowed.
QTc > 480 ms on screening ECG (using the Fredericia formula)
Leptomeningeal metastases as the only site of CNS metastases. Patients with parenchymal brain metastases and leptomeningeal metastases are eligible provided they meet all other eligibility criteria.
Concurrent treatment with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.).
Presence of active gastrointestinal (GI) disease or other condition that in the opinion of the investigator will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, or vomiting).
Previous treatment with cabazitaxel.
Concurrent use of St. John's wort and grapefruit/grapefruit juice ≤7 days prior to starting study drug is not allowed.
Known hypersensitivity to cabazitaxel or other drugs formulated with polysorbate 80.
Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting in the past 6 months
Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
Presence of other active cancers, or history of treatment for invasive cancer ≥3 years. Patients with stage I cancer who have received definitive local treatment with curative intent at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
Active (acute or chronic) or uncontrolled severe infections.
Symptomatic congestive heart failure (CHF) of New York Heart Association Class III or IV.
Active hepatic or biliary disease (except for patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment).

Summary

Conditions
Metastatic Breast Cancer With Intracranial Metastases
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. Through the safety lead-in portion of this trial we will define the optimal dose of cabazitaxel when given in combination with lapatinib for patients with HER2-positive MBC and CNS metastases. The Phase II portion wi...

This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. Through the safety lead-in portion of this trial we will define the optimal dose of cabazitaxel when given in combination with lapatinib for patients with HER2-positive MBC and CNS metastases. The Phase II portion will further assess intracranial response rate in patients with HER2-positive MBC and CNS metastases. Toxicity and progression free survival (PFS) will be obtained and evaluated. The trial will be conducted at multiple study sites by SCRI Development Innovations.

Inclusion Criterias

Left-ventricular-ejection fraction (LVEF) of ≥50% by an echocardiogram (ECHO) or by a multiple-gated acquisition (MUGA)
Serum potassium ≥ the institutional LLN
Adequate coagulation parameters.
...
Left-ventricular-ejection fraction (LVEF) of ≥50% by an echocardiogram (ECHO) or by a multiple-gated acquisition (MUGA)
Serum potassium ≥ the institutional LLN
Adequate coagulation parameters.
Ability to swallow oral medications.
Patients with brain metastases previously treated with WBRT/partial brain radiation only must have at least one intracranial tumor lesion ≥ 5mm and must have evidence of intracranial progressive disease
Patients with brain metastases previously untreated with any intracranial radiation (i.e., no whole brain radiation therapy [WBRT]/partial brain radiation or stereotactic radiosurgery [SRS]) must have at least one intracranial tumor lesion that is ≥ 5mm.
Patients who have received WBRT/partial brain radiation for intra-cranial metastases are eligible if treatment was completed ≥28 days prior to the first dose of study drug.
Patient must be discontinued from hormonal therapy a minimum of 1 day prior to the first dose of study treatment.
Patients must be neurologically stable, and if receiving steroids, must be on stable or decreasing doses of corticosteroids and/or anticonvulsants for defined as being on stable low doses of corticosteroids ≥ 5 days prior to the first dose of study treatment.
Immunohistochemical (IHC) score 3+ or
Willingness and ability to comply with trial and follow-up procedures.
Patients with HER2-positive MBC and unequivocal evidence of brain metastases.
Life expectancy ≥12 weeks.
Male patients willing to use adequate contraceptive measures.
Patients must have recovered (>2 week recovery is mandated) from any acute neurosurgical intervention for metastatic CNS disease (e.g., resection, shunt placement) and must be clinically stable. These patients must have residual measurable CNS lesion(s) following the surgical procedure if this site is to serve as the target lesion.
Ability to understand the nature of this trial and give written informed consent.
Serum magnesium ≥ the institutional lower limit of normal (LLN)
Patients previously treated with WBRT/partial brain radiation and SRS must have at least one intracranial tumor lesion ≥ 5mm that was not treated with SRS and must have intracranial disease.
IHC score 1-2+ and confirmed as FISH (Fluorescence in situ hybridization) positive (based on ASCO-CAP guidelines 2013) or
Patients receiving palliative radiation to bone, soft tissue or any other disease sites must have completed this ≥1 week prior to the first dose of study treatment.
Patients with brain metastases previously untreated with any intra-cranial radiation (i.e. no whole brain radiation therapy [WBRT]/partial brain radiation or stereotactic radiosurgery [SRS]) must have at least one intra-cranial tumor lesion that is ≥ 5mm.
Patients previously treated with SRS must either demonstrate disease progression ≥ 12 weeks after completing SRS with a lesion measuring ≥ 5mm or must have at least one intracranial tumor lesion ≥ 5mm that was not treated with SRS.
Patient must have completed biologic therapy ≥3 weeks or 5-half lives whichever is shorter.
Patient must have received prior treatment with HER2-directed therapy such as trastuzumab, either in the adjuvant or metastatic setting.
Patients without prior chemotherapy for MBC are eligible provided the patients relapsed during adjuvant therapy with trastuzumab or ≤6 months following completion of adjuvant therapy. Otherwise, there is no specific minimum or maximum number of previous chemotherapy regimens for MBC.
Prior treatment with lapatinib in the (neo)adjuvant and metastatic setting.
Estrogen receptor (ER) and progesterone receptor (PR) status in the primary or most recent tumor assessment must be known or pending at the time of study registration. Patient's ER/PR status (i.e., positive or negative) does not influence enrollment but is a requirement.
Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of treatment.
Adequate hematologic, renal, and hepatic function.
FISH or ISH (in situ hybridization) positive (based on ASCO-CAP guidelines 2013)
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2.

Exclusion Criterias

Peripheral neuropathy ≥Grade 2 (CTCAE v4.0).
Concurrent treatment with radiation therapy, hormonal therapy, biologic therapy or chemotherapy is not allowed. Low dose corticosteroids (≤30 mg/day prednisone or its equivalent) are allowed.
QTc > 480 ms on screening ECG (using the Fredericia formula)
...
Peripheral neuropathy ≥Grade 2 (CTCAE v4.0).
Concurrent treatment with radiation therapy, hormonal therapy, biologic therapy or chemotherapy is not allowed. Low dose corticosteroids (≤30 mg/day prednisone or its equivalent) are allowed.
QTc > 480 ms on screening ECG (using the Fredericia formula)
Leptomeningeal metastases as the only site of CNS metastases. Patients with parenchymal brain metastases and leptomeningeal metastases are eligible provided they meet all other eligibility criteria.
Concurrent treatment with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.).
Presence of active gastrointestinal (GI) disease or other condition that in the opinion of the investigator will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, or vomiting).
Previous treatment with cabazitaxel.
Concurrent use of St. John's wort and grapefruit/grapefruit juice ≤7 days prior to starting study drug is not allowed.
Known hypersensitivity to cabazitaxel or other drugs formulated with polysorbate 80.
Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting in the past 6 months
Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
Presence of other active cancers, or history of treatment for invasive cancer ≥3 years. Patients with stage I cancer who have received definitive local treatment with curative intent at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
Active (acute or chronic) or uncontrolled severe infections.
Symptomatic congestive heart failure (CHF) of New York Heart Association Class III or IV.
Active hepatic or biliary disease (except for patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment).

Locations

Cincinnati, Ohio, 45242
Nashville, Tennessee, 37203
Saint Petersburg, Florida, 33705
Fort Myers, Florida, 33916
...
Cincinnati, Ohio, 45242
Nashville, Tennessee, 37203
Saint Petersburg, Florida, 33705
Fort Myers, Florida, 33916

Tracking Information

NCT #
NCT01934894
Collaborators
  • Novartis
  • GlaxoSmithKline
  • Sanofi
Investigators
Study Chair: Denise A. Yardley, MD SCRI Development Innovations