Clinical trial NCT00444535: Lapatinib and Bevacizumab for Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Breast
Keywords: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-03-08
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Investigator-evaluated Crude Progression-free Survival Rate After 12 Weeks of Study Treatment
timeFrame: up to week 12
Secondary outcomes:
measure: Overall Tumor Response - Best Response Per Investigator Assessment (RECIST)
timeFrame: 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.
measure: Overall Tumor Response Rate Per Investigator Assessment (RECIST)
timeFrame: 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.
measure: Investigator-Assessed Clinical Benefit Response Rate (%) (RECIST)
timeFrame: 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.
measure: Progression-free Survival
timeFrame: 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.
measure: Progression-free Survival - Kaplan-Meier Estimates for Progression-free Survival (Weeks) - Median
timeFrame: 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.
measure: Progression-free Survival - Kaplan-Meier Estimates for Progression-free Survival (Weeks) - 1st and 3rd Quartile
timeFrame: 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.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Hollywood
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Basking Ridge
country: United States
facility: Novartis Investigative Site
state: New York
city: Commack
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Rockville Centre
country: United States
facility: Novartis Investigative Site
state: New York
city: Sleepy Hollow
country: United States
facility: Novartis Investigative Site
state: New York
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Rugo HS, Chien AJ, Franco SX, Stopeck AT, Glencer A, Lahiri S, Arbushites MC, Scott J, Park JW, Hudis C, Nulsen B, Dickler MN. A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat. 2012 Jul;134(1):13-20. doi: 10.1007/s10549-011-1918-z. Epub 2011 Dec 24.