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Lapatinib

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* Cabazitaxel 1-hour IV infusion on Day 1 of each 3 week cycle (dose to be determined)
* Lapatinib PO once daily (dose to be determined)

Treatment cycles will be repeated every 3 weeks.

cabazitaxel

lapatinib

Denise A. Yardley, MD

This phase II trial will combine two agents, cabazitaxel and lapatinib, to treat patients with metastatic breast cancer (MBC) which has metastasized to the brain. The first portion of the study will determine the optimal dose of the cabazitaxel/lapatinib combination to administer to patients. After determining the optimal dose, patients will continue treatment with cabazitaxel and lapatinib to assess response to treatment with these agents.

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.

Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases

Phase II Study With Lead-in Safety Cohort of Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases

The number of patients with Complete and Partial Response (CR+PR) of CNS lesions assessed per modified RECIST Criteria for Evaluation of Intracranial Disease. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.

The maximum tolerated dose (MTD) of cabazitaxel and lapatinib will be determined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. A listing of DLTs are reported in the subsequent Primary Outcome Measure.

During the safety lead-in, a standard 3+3 dose escalation design is used to determine the maximum tolerated dose (MTD) of cabazitaxel with lapatinib. The MTD would be determined by the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during 1 cycle (21 days) of therapy. If 2 of 6 patients within a dose level experiences a DLT, that dose level would be defined as exceeding the MTD and the previous dose level would be evaluated. DLTs are assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.

The number of patients with Complete Response, Partial Response or Stable Disease extending beyond 6 months (CR+PR+SD ≥ 6 months), determined by RECIST v1.1. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion; SD=Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since the treatment started.

The number of participants having Complete and Partial Responses (CR+PR) of extra-cranial lesions assessed per RECIST v1.1 Criteria. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.

Evaluate the three and six-month CNS progression free survival measured from date of first protocol treatment until tumor progression or death.

Novartis

GlaxoSmithKline

Sanofi

SCRI Development Innovations, LLC

Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.

Cabazitaxel: 20 mg/m\^2, 1-hour IV infusion on Day 1 of each 3 week cycle, Lapatinib: 1000 mg by mouth (PO) once daily

Dose Level 1 (20 mg/m^2 Cabazitaxel + Lapatinib)

Cabazitaxel: 25 mg/m\^2, 1-hour IV infusion on Day 1 of each 3 week cycle, Lapatinib: 1000 mg by mouth (PO) once daily

Dose Level 2 (25 mg/m^2 Cabazitaxel + Lapatinib)

Cabazitaxel: 20 mg/m2, 1-hour IV infusion on Day 1 of each 3 week cycle, Lapatinib: 1000 mg by mouth (PO) once daily

Dose Level 1 (20 mg/m2 Cabazitaxel + Lapatinib)

Cabazitaxel: 25 mg/m2, 1-hour IV infusion on Day 1 of each 3 week cycle, Lapatinib: 1000 mg by mouth (PO) once daily

Dose Level 2 (Level 1 (25 mg/m2 Cabazitaxel + Lapatinib)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Includes participants that received at least one dose of study treatment.

Early termination of study resulted in small number of subjects analyzed.

Charles Davis, RAC

CNS Objective Response

Cabazitaxel: (at Dose Level 1, 20 mg/m\^2 or at Dose Level 2, 25 mg/m\^2), 1-hour IV infusion on Day 1 of each 3 week cycle, Lapatinib: 1000 mg by mouth (PO) once daily

Cabazitaxel and Lapatinib

Includes all treated participants, either at Dose Level 1 or Dose Level 2

Maximum Tolerated Dose of Cabazitaxel With Lapatinib

febrile neutropenia

neutropenia

diarrhea

septic shock

Cabazitaxel: 20 mg/m\^2: 1-hour IV infusion on Day 1 of each 3 week cycle, Lapatinib: 1000 mg by mouth (PO) once daily

Dose Level 1

Cabazitaxel 25mg/m\^2:: 1-hour IV infusion on Day 1 of each 3 week cycle, Lapatinib: 1000 mg by mouth (PO) once daily

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases	NCT01934894	Metastatic Brea...	cabazitaxel lapatinib	18 Years -	SCRI Development Innovations, LLC
Cabazitaxel Plus Lapatinib as Therapy for HER2-Positive Metastatic Breast Cancer Patients With Intracranial Metastases	NCT01934894	Metastatic Brea...	cabazitaxel lapatinib	18 Years -	SCRI Development Innovations, LLC

Spots Global Cancer Trial Database for intracranial metastases