Phase II Study of SKI-606 in Subjects with Advanced or Metastatic Breast Cancer

• Conditions: Approx. 8-11% of all women will develop breast cancer in their lives. Nearly half of the women who develop breast cancer also develop metastatic disease. The average survival time from diagnosis to recurrence for these patients ranges from approx. 18-30 months, the 5-year survival rate is only 21%. HER2 overexpression (usually correlated with aggressive disease and decreased survival) occurs early in the pathogenesis of breast cancer in approx. 15% to 25% of patients with metastatic disease.

• Registration Number: EUCTR2005-005543-25-MT
• Lead Sponsor: Wyeth Research Division

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-08-21
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

- Women > 18 years of age.
- Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV (as defined by the American Joint Committee on Cancer), not curable with available therapy.
- Relapsed or refractory after 1 to 3 prior chemotherapy regimens for advanced or metastatic disease.
- At least one measurable lesion, measuring > 20 mm.
- Karnofsky Performance Status of > 70%, and not declining within 4 weeks before first dose.
- Life expectancy of at least 16 weeks.
- Adequate hepatic, renal and bone marrow function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Chemotherapy, immunotherapy, surgery, hormone therapy, radiation therapy or any other anti-cancer therapy, within 2 weeks prior to dose day 1.
- Use of, or requirement for, bisphosphonates within 8 weeks prior to screening.
- Any other cancer within 5 years of screening (except basal cell carcinoma or cervical CIS)§Subjects with a history of prior stem cell transplant.
- Prior therapy with SKI-606 or any other Src kinase inhibitor.
- Extensive visceral disease as defined in the protocol
- Subjects with skin or bone as the only site of disease.
- Subjects with a history of CNS metastases will be eligible if the metastases have been treated with either RT or surgical resection and subjects are asymptomatic for three months, and no longer requiring steroids.
- An ongoing clinical requirement for administration of strong inhibitors of CYP-3A4.
- Needing frequent or continuous use of therapeutic doses of systemic steroids during the 6 months preceding screening.
- A left ventricular ejection fraction of less than 50% measured by multigated imaging of the heart (MUGA) or echocardiogram (ECHO).
- A History of clinically significant or uncontrolled cardiac disease including CHF (as defined by NY Heart Association 3 & 4), angina, MI, arrhythmia, prolonged QTc (>0.47 sec), or unexplained syncope.
- Concomitant use or need for medications known to prolong the QTc interval.
- A history of hypercalcemia within 2 weeks prior to screening.
- History of serum postassium > 5.5 mEq/L within 2 weeks prior to screening
- Uncorrected hypomagnesia or hypokalemia due to potential effects on the QT interval.
- Prior treatment with anthracyclines with a cumulative dose of > 400 mg/m2 of doxorubicin or equivalent.
- Subjects known to be HIV (human immunodeficiency virus) seropositive and/or acute or chronic hepatitis B (HbsAg positive) or C (anti-HCV positive).
- Pregnant or breastfeeding women or women of childbearing potential who are not using effective contraception.
- Recent (within 30 days of first dose) or ongoing clinically significant gastrointestinal disorder (e.g. malabsorption, short bowel syndrome, bleeding).
- Any other major illness that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Determine the rate of progression free survival (PFS) at 16 weeks.;Secondary Objective: - Determine safety profile of 400 mg/day in this patient population<br>- Determine rate of objective response (complete response + partial response) within 1 year.<br>- Determine survival rate at 3 years after beginning SKI-606 treatment.<br>- Determine the population PK of SKI-606 in this patient population.;Primary end point(s): The primary efficacy endpoint is progression free survival at 16 weeks (PFS16). The interesting rate will be 40% with an uninteresting rate of 20%