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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00455039
Recruitment Status : Completed
First Posted : April 3, 2007
Last Update Posted : May 12, 2016
Information provided by (Responsible Party):
University of New Mexico

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: GW572016 Phase 1 Phase 2

Detailed Description:
See above.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INST 0514C- A Neoadjuvant Phase II Trial of GW572016 in HER2 Overexpressing Breast Cancer Patients: Biologic Correlative Study
Study Start Date : July 2005
Actual Primary Completion Date : October 2009
Actual Study Completion Date : October 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Intervention Details:
  • Drug: GW572016
    Dose: 1500 mg daily

Primary Outcome Measures :
  1. The primary end point of this study is clinical efficacy of GW572016 in treatment naïve patients with locally advanced breast cancer. [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. The secondary end points would be the biologic correlative of relevant biomarkers. [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. All patients must be female.
  2. Signed informed consent.
  3. 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.
  4. 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.
  5. Negative serum pregnancy test (beta-HCG) within 7 days of starting study, if of child-bearing potential.
  6. Kidney and liver function tests - all within 1.5 times the institution's upper limit of normal.
  7. Performance status (WHO scale) <2 and life expectancy >6 months.
  8. Age >18 years.
  9. No brain or leptomeningeal disease.
  10. 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.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00455039

United States, New Mexico
Albuquerque, New Mexico, United States, 87106
Sponsors and Collaborators
University of New Mexico
Principal Investigator: Melanie Royce, MD University of New Mexico Cancer Center

Responsible Party: University of New Mexico Identifier: NCT00455039     History of Changes
Other Study ID Numbers: INST 0514C
First Posted: April 3, 2007    Key Record Dates
Last Update Posted: May 12, 2016
Last Verified: May 2016

Keywords provided by University of New Mexico:
neoadjuvant, HER2, Breast,GSK,lapatinib

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action