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”

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole may fight breast cancer by blocking the use of estrogen by the tumor cells.

Lonafarnib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. It is not yet known whether giving anastrozole with lonafarnib is more effective than giving anastrozole with placebo in treating breast cancer.

PURPOSE: This randomized phase II trial is studying anastrazole given with lonafarnib to see how this regimen works compared to anastrozole given with placebo in treating postmenopausal women with stage IIIB, stage IIIC, or stage IV breast cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

OBJECTIVES:

Primary - Compare progression-free survival of postmenopausal women with hormone receptor-positive stage IIIB, IIIC, or IV breast cancer treated with anastrozole in combination with lonafarnib vs placebo.

Secondary - Compare the objective response rate in patients treated with these regimens. - Compare duration of response in patients treated with these regimens. - Compare overall survival of patients treated with these regimens. - Determine exposure to these regimens in these patients. - Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral anastrozole once daily and oral lonafarnib twice daily on days 1-28. - Arm II: Patients receive oral anastrozole once daily and oral placebo twice daily on days 1-28.

In both arms courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 4 weeks until disease progression and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A maximum of 110 patients (55 per treatment arm) will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: anastrozole
• Drug: lonafarnib

Primary Measures

• Progression-free survival
  • Safety Issue?: No

Secondary Measures

• Objective response rate
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No
• Duration of response
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer
• Stage IIIB, IIIC, or IV disease
• Measurable or evaluable disease
• Measurable disease defined as masses with clearly defined margins AND at least 1 diameter ≥ 20 mm by radiography OR ≥ 10 mm by spiral CT scan
• Evaluable disease defined as masses without clearly defined margins on radiological images OR no diameter ≥ 20 mm
• Patients with bone only disease eligible if disease is evaluable
• No brain metastases
• Hormone receptor status:
• Estrogen receptor- and/or progesterone receptor-positive

PATIENT CHARACTERISTICS:

• Age
• Postmenopausal
• Sex
• Female
• Menopausal status
• Postmenopausal
• Performance status
• ECOG 0-1
• Life expectancy
• Not specified
• Hematopoietic
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10.0 g/dL
• Hepatic
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Renal
• Creatinine ≤ 1.5 times ULN
• Cardiovascular
• No significant QTcF prolongation (i.e., QTcF ≥ 470 msec)
• Other
• No situation or condition that would preclude study participation
• No known or suspected hypersensitivity to any excipients of lonafarnib (e.g., povidone, poloxamer 188, croscarmellose sodium, silicon dioxide, or magnesium stearate)

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• No prior or concurrent biologic therapy
• No prior or concurrent immunotherapy
• Chemotherapy
• Prior adjuvant chemotherapy allowed provided the disease-free interval from completion of treatment to diagnosis of advanced or metastatic disease is ≥ 12 months
• No prior chemotherapy for advanced disease
• No concurrent chemotherapy
• Endocrine therapy
• Prior adjuvant tamoxifen allowed provided the disease-free interval from completion of treatment to diagnosis of advanced or metastatic disease is ≥ 12 months
• No prior hormonal therapy for advanced disease
• No prior aromatase inhibitors
• More than 2 days since prior and no concurrent high-dose chronic steroids
• No concurrent hormone replacement therapy
• No other concurrent hormonal therapy
• Radiotherapy
• Prior radiotherapy allowed
• No concurrent radiotherapy except palliative radiotherapy for bone metastasis
• Surgery
• Not specified
• Other
• More than 30 days since prior investigational drugs
• No prior farnesyl transferase inhibitors
• More than 2 days since prior and no concurrent use of any of the following inducers or inhibitors of CYP3A4:
• Ethinyl estradiol
• Gestodene
• Itraconazole
• Ketoconazole
• Cimetidine
• Erythromycin
• Carbamazepine
• Phenobarbital
• Phenytoin
• Rifampin
• Sulfinpyrazone
• No concurrent participation in another clinical trial
• No other concurrent investigational therapy

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: Jonsson Comprehensive Cancer Center

Overall Clinical Trial Officials and Contacts

John A. Glaspy, MD, MPH Principal Investigator Jonsson Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00098904

Study ID Number: CDR0000396775

ClinicalTrials.gov Identifier: NCT00098904

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database