Lapatinib and Bevacizumab for Metastatic Breast Cancer

NCT00444535 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: EGF103890CLAP016A2201
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 9

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Tumor Response - Best Response Per Investigator Assessment (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)

  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)

  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

  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

  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.

Study Arms (1)

Oral lapatinib tablets in combination with IV bevacizumab

EXPERIMENTAL

1500 mg oral lapatinib (once daily) plus 10 mg/kg intravenous bevacizumab (every two weeks)

Drug: lapatinib; Drug: bevacizumab

Interventions

lapatinib DRUG

1500 mg oral lapatinib (once daily)

Also known as: Tykerb/Tyverb

Oral lapatinib tablets in combination with IV bevacizumab

bevacizumab DRUG

10 mg/kg intravenous bevacizumab (every two weeks)

Oral lapatinib tablets in combination with IV bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Tucson, Arizona, 85724, United States

Location

Novartis Investigative Site

San Francisco, California, 94115, United States

Location

Novartis Investigative Site

Hollywood, Florida, 33021, United States

Location

Novartis Investigative Site

Tampa, Florida, 33612, United States

Location

Novartis Investigative Site

Basking Ridge, New York, 07920, United States

Location

Novartis Investigative Site

Commack, New York, 11725, United States

Location

Novartis Investigative Site

New York, New York, 10065, United States

Location

Novartis Investigative Site

Rockville Centre, New York, 11570, United States

Location

Novartis Investigative Site

Sleepy Hollow, New York, 10591, United States

Location

Related Publications (1)

• 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.

  PMID: 22198412 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Osteitis Deformans

Interventions

Lapatinib; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

8620778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2007
• First Posted: March 8, 2007
• Study Start: February 27, 2007
• Primary Completion: July 22, 2008
• Study Completion: June 19, 2020
• Last Updated: October 25, 2021
• Results First Posted: August 20, 2009

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

US (9)