Lapatinib and Bevacizumab for Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study will examine the efficacy and safety of lapatinib and bevacizumab in patients with ErbB2-overexpressing breast cancer.

Official Title
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A Phase II, Open-Label Study of the Clinical Activity, Safety, and Tolerability of Lapatinib in Combination With Bevacizumab in Subjects With Advanced or Metastatic ErbB2-Overexpressing Breast Cancer

Conditions
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Neoplasms, Breast

Intervention / Treatment
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* Drug: lapatinib
* Drug: bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Females that are at least 18 years of age. Women of childbearing potential must have a negative serum pregnancy test at screening. Documented evidence of HER2-overexpressing unresectable or metastatic breast cancer. Disease may/may not have been treated in metastatic setting. Subjects are permitted (but not required) to have previously-treated brain metastases that are stable and asymptomatic. Adequate hepatic, renal and cardiac function ECOG score 0-1 and a life expectancy of at least 12 weeks. Able to swallow oral medication Signed informed consent Exclusion criteria: Pregnancy Unstable or symptomatic CNS metastases Major surgery within 28 days of enrollment (minor surgery within 7 days). Prior anti-cancer treatment within 14 days of enrollment, or unresolved treatment-related toxicities. A serious non-healing wound, ulcer, or bone fracture at baseline. Class II, III or IV heart failure as defined by the NYHA functional classification system History of significant vascular disease, arterial thrombosis, unstable INR, hypertensive crisis, or uncontrolled hypertension. History of myocardial infarction, stenting procedure, or angioplasty within 6 months of enrollment. History of abdominal fistulae, gastrointestinal perforation, or intra-abdominal abscess within 6 months of enrollment. History of malabsorption syndrome, ulcerative colitis, or bowel obstruction. Proteinuria Requires concurrent anti-cancer treatment or investigational treatment. Known hypersensitivity to either study medication Received investigational treatment within 28 days or 5 half-lives, whichever is longer Concurrent disease or circumstances that would lead the investigator would consider the subject an inappropriate candidate for the study Requires medication that has been excluded during study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral lapatinib tablets in combination with IV bevacizumab<br>1500 mg oral lapatinib (once daily) plus 10 mg/kg intravenous bevacizumab (every two weeks) | Drug: lapatinib<br>* 1500 mg oral lapatinib (once daily)<br>* Other names: Tykerb/Tyverb;Drug: bevacizumab<br>* 10 mg/kg intravenous bevacizumab (every two weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-evaluated Crude Progression-free Survival Rate After 12 Weeks of Study Treatment | The PFS rate is defined as the percentage of subjects who have shown no evidence of disease progression or death from any cause following 12 weeks of treatment. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Since there is no independent reviewer, only the investigator response was reported. | up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Tumor Response - Best Response Per Investigator Assessment (RECIST) | Overall Tumor Response - Best Response per Investigator Assessment Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by image including CT, MRI or bone scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. For each subject, the best tumor response during the study was considered to be the 'Overall Tumor Response' per the Response Evaluation Criteria in Solid Tumors (RECIST). | This endpoint was defined in the original protocol but was cancelled per Amendment 3, which was implemented Nov 2015. The timeframe therefore is from treatment start to Nov 2015, with a maximum timeframe of approx. 8.7 years. | 
| Overall Tumor Response Rate Per Investigator Assessment (RECIST) | Overall Tumor Response Rate is defined as the percentage of subjects achieving either a confirmed complete (CR) or partial (PR) tumor response by investigator and per the Response Evaluation Criteria in Solid Tumors (RECIST). For each subject, the best tumor response during the study are considered the 'Overall Tumor Response.' Subjects with unknown or missing response are treated as non-responders; i.e. they are included in the denominator when calculating the percentage. | This endpoint was defined in the original protocol but was cancelled per Amendment 3, which was implemented Nov 2015. The timeframe therefore is from treatment start to Nov 2015, with a maximum timeframe of approx. 8.7 years. | 
| Investigator-Assessed Clinical Benefit Response Rate (%) (RECIST) | Clinical Benefit Rate is defined as the percentage of subjects with evidence of confirmed complete or partial tumor responses at any time or stable disease for at least 24 weeks per the Response Evaluation Criteria in Solid Tumors (RECIST). Subjects with unknown or missing response are treated as non-responders (i.e. not Complete response (CR), Partial response (PR) or Stable Disease (SD)). | This endpoint was defined in the original protocol but was cancelled per Amendment 3, which was implemented Nov 2015. The timeframe therefore is from treatment start to Nov 2015, with a maximum timeframe of approx. 8.7 years. | 
| Progression-free Survival | Progression-free survival (PFS) = time from treatment start date until the first documented sign of disease progression, as defined by the investigator, or death due to any cause. For participants who did not progress or die at the time of reporting, PFS data were censored at the time of the last radiological assessment. | This endpoint was defined in the original protocol but was cancelled per Amendment 3, which was implemented Nov 2015. The timeframe therefore is from treatment start to Nov 2015, with a maximum timeframe of approx. 8.7 years. | 
| Progression-free Survival - Kaplan-Meier Estimates for Progression-free Survival (Weeks) - Median | Progression-free survival (PFS) = time from treatment start date until the first documented sign of disease progression, as defined by the investigator, or death due to any cause. For participants who did not progress or die at the time of reporting, PFS data were censored at the time of the last radiological assessment. Greenwood's formula was used to calculate the standard error of the estimates from the Kaplan-Meier curve. | This endpoint was defined in the original protocol but was cancelled per Amendment 3, which was implemented Nov 2015. The timeframe therefore is from treatment start to Nov 2015, with a maximum timeframe of approx. 8.7 years. | 
| Progression-free Survival - Kaplan-Meier Estimates for Progression-free Survival (Weeks) - 1st and 3rd Quartile | Progression-free survival (PFS) = time from treatment start date until the first documented sign of disease progression, as defined by the investigator, or death due to any cause. For participants who did not progress or die at the time of reporting, PFS data were censored at the time of the last radiological assessment. Greenwood's formula was used to calculate the standard error of the estimates from the Kaplan-Meier curve. | This endpoint was defined in the original protocol but was cancelled per Amendment 3, which was implemented Nov 2015. The timeframe therefore is from treatment start to Nov 2015, with a maximum timeframe of approx. 8.7 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VEGF, Tyrosine kinase, ErbB2, Her2-neu, metastatic breast cancer, EGFR, ErbB1, bevacizumab, lapatinib, breast carcinoma, breast cancer, breast lump, breast cancer positive for human epidermal growth factor receptor 2 (HER2), HER2 positive metastatic breast cancer, breast cancer progression, estrogen-receptor (ER) positive(+) breast cancer, Paget's disease