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

• Sponsor: University of New Mexico (Other)
• Overall Status: Completed
• CT.gov ID: NCT00455039
• Collaborator: (none)
• Enrollment: 55
• Location: 1
• Duration (Months): 51
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: N/A
• 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: Jul 1, 2005
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Outcome Measures

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. [3 years]

Secondary Outcome Measures

1. The secondary end points would be the biologic correlative of relevant biomarkers. [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• 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.

1. Negative serum pregnancy test (beta-HCG) within 7 days of starting study, if of child-bearing potential.

2. Kidney and liver function tests - all within 1.5 times the institution's upper limit of normal.

3. Performance status (WHO scale) <2 and life expectancy >6 months.

4. Age >18 years.

5. No brain or leptomeningeal disease.

6. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UNM CRTC	Albuquerque	New Mexico	United States	87106

Sponsors and Collaborators

• University of New Mexico

Investigators

• Principal Investigator: Melanie Royce, MD, University of New Mexico Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of New Mexico
• ClinicalTrials.gov Identifier: NCT00455039
• Other Study ID Numbers: INST 0514C
• First Posted: Apr 3, 2007
• Last Update Posted: May 12, 2016
• Last Verified: May 1, 2016

• Keywords provided by University of New Mexico: neoadjuvant, HER2, Breast,GSK,lapatinib
• Additional relevant MeSH terms: Breast Neoplasms; Lapatinib

Study Results

No Results Posted as of May 12, 2016