Anastrozole Plus Lonafarnib (SCH 66336) or Plus Placebo for the Treatment of Advanced Breast Cancer (P03480)

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 Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Placebo; Drug: anastrozole; Drug: Lonafarnib

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lonafarnib plus Anastrozole; Participants receive lonafarnib 200 mg orally (PO) twice per day (BID) beginning on Day 1 Cycle 1 and continuing until Progression of Disease, unacceptable toxicity, or other discontinuation criteria are met; and anastrozole 1 mg, PO, once per day (QD) for as long as the participant is receiving lonafarnib	Drug: anastrozole; Drug: Lonafarnib; Other Names: SCH 66336
ACTIVE_COMPARATOR: Placebo plus Anastrozole; Participants receive placebo to lonafarnib PO BID beginning on Day 1 Cycle 1 until Progression of Disease, unacceptable toxicity, or other discontinuation criteria are met; and anastrozole, 1mg PO QD for as long as the participant is receiving placebo	Drug: Placebo; Drug: anastrozole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS)	When approximately 70 subjects have progressed

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (ACTUAL): May 1, 2009
• Study Completion (ACTUAL): May 1, 2009

Study Registration Dates

• First Submitted: April 14, 2004
• First Submitted That Met QC Criteria: April 15, 2004
• First Posted (ESTIMATE): April 16, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): April 15, 2015
• Last Update Submitted That Met QC Criteria: March 26, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole; Lonafarnib
• Other Study ID Numbers: P03480