INST 0514C- Biologic Correlative Study: Trial of GW572016 in HER2 Overexpressing Breast Cancer Patients

NCT00455039 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: INST 0514C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant chemotherapy has become the standard of care for breast cancer patients with large tumors in order to render them operable for mastectomy or, in some cases, for lumpectomy and radiation therapy. Building on this theme, several large hormonal therapies are extensively investigated in the neoadjuvant setting, together with biologic correlates for response and resistance. As a further extension, neoadjuvant therapies with biologic agents are now too, being investigated for biologic evidence of efficacy before large-scale clinical trials of thousands of patients are embarked on. The neoadjuvant setting is especially attractive for these studies for several reasons including early assessment of response to therapy, biopsiable access to the primary tumor, and considerable reduced sample sizes compared to those required in the adjuvant setting. In addition, clinical response to neoadjuvant chemotherapy is a validated surrogate marker for improved survival. It may be used to test the overall efficacy of neoadjuvant treatment regimens and mirrors the effect of therapy on micrometastases setting. In a recent study, good clinical response to neoadjuvant chemotherapy was the only independent variable, by multivariate analysis, associated with decreased risk of death. GW572016 is a new and promising dual tyrosine kinase inhibitor against HER1/2. Hundreds of patients were treated in phase I and II studies world-wide and results indicate that this reversible, oral small molecule is generally well-tolerated. Studies of neoadjuvant Trastuzumab indicate that HER2 interference leads to significant tumor regression even after 3 weeks of monotherapy. We aim to extend these findings with a novel agent, GW572016 that may be more effective, especially from its in vitro data, and to discover the true response rate to inhibiting HER1/2 signal transduction in breast cancer patients.

Conditions

Breast Cancer

Keywords

neoadjuvant; HER2; Breast; lapatinib; GSK

Outcome Measures

Primary Outcomes (1)

• The primary end point of this study is clinical efficacy of GW572016 in treatment naïve patients with locally advanced breast cancer.

  3 years

Secondary Outcomes (1)

• The secondary end points would be the biologic correlative of relevant biomarkers.

  3 years

Study Arms (1)

GW572016 1500mg

EXPERIMENTAL

patients received GW572016 1500mg daily

Drug: GW572016

Interventions

GW572016 DRUG

Dose: 1500 mg daily

GW572016 1500mg

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must be female.
• Signed informed consent.
• Only subjects with Stage IIIa, IIIb, IIIc, or IV disease should be enrolled in this trial. Locally advanced breast cancers of clinical and or radiologic size greater than or equal to 3 cm, or primary breast cancers with concomitant gross metastatic disease.
• HER2 overexpressing tumors defined as HercepTest score of 3+, or \> 10% cells moderately or strongly HER2 positive by other methods, or semi-quantitative score of \>5 (in Dr. Allred's laboratory) or gene amplified.
• Negative serum pregnancy test (beta-HCG) within 7 days of starting study, if of child-bearing potential.
• Kidney and liver function tests - all within 1.5 times the institution's upper limit of normal.
• Performance status (WHO scale) \<2 and life expectancy \>6 months.
• Age \>18 years.
• No brain or leptomeningeal disease.
• No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.

You may not qualify if:

• Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
• Severe underlying chronic illness or disease.
• Cardiomyopathy or baseline LVEF \<50%.
• Other investigational drugs while on study.
• Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

UNM CRTC

Albuquerque, New Mexico, 87106, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Melanie Royce, MD

  University of New Mexico Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2007
• First Posted: April 3, 2007
• Study Start: July 31, 2023
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-07

Locations

US (1)