Official Title: “A Randomized Double-Blind Phase-2 Study of Anastrozole Plus Lonafarnib (SCH 66336) or Anastrozole Plus Placebo for the Treatment of Subjects With Advanced Breast Cancer”

Primary Objective(s): - To compare the activity (progression-free survival [PFS]) of anastrozole in combination with lonafarnib to that of anastrozole in combination with placebo in subjects with hormone-sensitive ADVANCED breast cancer.

Secondary Objective(s): - To determine the effects of anastrozole in combination with lonafarnib on objective response, duration of response, overall survival, and safety in subjects with advanced breast cancer. To assess the exposure and pharmacokinetics of lonafarnib and anastrozole in the subject population.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2008

Intervention(s) in this Clinical Trial

• Drug: Lonafarnib plus Anastrozole
  • Lonafarnib 200 mg PO BID beginning on Cycle 1 Day 1 and continuously until Progression of Disease, unacceptable toxicity, or other discontinuation criteria. Subjects will be treated concomitantly with anastrozole (1 mg PO QD) continuously.
• Drug: Placebo plus Anastrozole
  • Placebo PO BID beginning on Cycle 1 Day 1 and continuously until Progression of Disease, unacceptable toxicity, or other discontinuation criteria. Subjects will be treated concomitantly with anastrozole (1 mg PO QD) continuously.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Lonafarnib plus Anastrozole
• Active Comparator: Placebo plus Anastrozole

Primary Measures

• Progression-free survival (PFS)
  • Time Frame: When approximately 70 subjects have progressed
    Safety Issue?: No

Secondary Measures

• Objective response rate (adjusted RECIST criteria), duration of response, and overall survival
  • Time Frame: When approximately 70 subjects have progressed
    Safety Issue?: Yes
• To access the exposure and pk of lonafarnib and anastrazole in the subject population.
  • Time Frame: When approximately 70 subjects have progressed
    Safety Issue?: Yes

Inclusion Criteria:

• Postmenopausal women who have histologically-confirmed breast cancer with the following characteristics:
• estrogen and/or progesterone receptor positive,
• locally advanced disease
• distant metastatic disease, stage 4
• Subjects eligible for single-agent treatment with aromatase inhibitors for current disease.
• Subjects taking biophosphonates are allowed if they begin bisphosphonate therapy AT
• LEAST two weeks prior to randomization.
• Measurable disease (masses with clearly defined margins on radiological images and at least one diameter >=20 mm[>=10 mm if spiral CT]) or evaluable disease (masses with margins not clearly defined on radiological images or with no diameter >= 20 mm).
• Subjects with bone disease only are permitted if disease is evaluable.
• ECOG Performance Status of 0 or 1.
• Sufficient bone marrow reserve.
• Adequate hepatic and renal function: laboratory values within protocol requirements.

Exclusion Criteria:

• Subjects who have received more than one regimen of cytotoxic chemotherapy for advanced disease.
• Subjects with with CLINICALLY APPARENT brain metastases or extensive visceral disease, including extensive hepatic involvement or pulmonary lymphangitic spread of tumor.
• Subjects with prior treatments with FTIs.
• Subjects with a known or suspected hypersensitivity to any excipients in the lonafarnib formulation (Providone, Poloxamer 188, croscarmellose sodium, silicon dioxide, and magnesium stearate).

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Antoine Yver, MD Study Director Schering-Plough  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00081510

Study ID Number: P03480

ClinicalTrials.gov Identifier: NCT00081510

Health Authority: United States: Food and Drug Administration