Lapatinib and Bevacizumab for Metastatic Breast Cancer

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

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

Study Overview

• Status: Completed
• Conditions: Neoplasms, Breast
• Intervention / Treatment: Drug: lapatinib; Drug: bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Novartis Investigative Site
  • California
    • San Francisco, California, United States, 94115
      • Novartis Investigative Site
  • Florida
    • Hollywood, Florida, United States, 33021
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33612
      • Novartis Investigative Site
  • New York
    • Basking Ridge, New York, United States, 07920
      • Novartis Investigative Site
    • Commack, New York, United States, 11725
      • Novartis Investigative Site
    • New York, New York, United States, 10065
      • Novartis Investigative Site
    • Rockville Centre, New York, United States, 11570
      • Novartis Investigative Site
    • Sleepy Hollow, New York, United States, 10591
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2007
• Primary Completion (Actual): July 22, 2008
• Study Completion (Actual): June 19, 2020

Study Registration Dates

• First Submitted: March 6, 2007
• First Submitted That Met QC Criteria: March 6, 2007
• First Posted (Estimate): March 8, 2007

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; bevacizumab; VEGF; EGFR; lapatinib; breast carcinoma; metastatic breast cancer; ErbB1; ErbB2; breast lump; HER2 positive metastatic breast cancer; breast cancer progression; estrogen-receptor (ER) positive(+) breast cancer; Paget's disease; Tyrosine kinase; breast cancer positive for human epidermal growth factor receptor 2 (HER2); Her2-neu
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Bevacizumab; Lapatinib
• Other Study ID Numbers: EGF103890; CLAP016A2201 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No