Lonafarnib in Metastatic Breast Cancer

A Phase II Study of Lonafarnib in Patients With Metastatic Breast Cancer

A published phase 2 study reported that lonafarnib was administered as a single agent via continuous or intermittent oral dosing to 76 women with advanced breast cancer who were previously treated with chemotherapy and/or with endocrine therapy. Objective response rates of approximately 10% were observed. This study will determine the rate of progression-free survival of patients with metastatic breast cancer who receive lonafarnib.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Lonafarnib

Detailed Description

OUTLINE: This is a multi-center study

Patients will be treated with lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator's discretion.

1 Cycle = 21 days of lonafarnib (plus the time required to recover from toxicity if encountered).

ECOG Performance Status 0-1

Life Expectancy: Not Specified

Hematopoietic:

• Platelets > 100 K/mm3
• Absolute Neutrophil Count (ANC) > 1.2 K/mm3
• Hemoglobin ≥ 9 g/dl
• Serum potassium ≥ 3.3 mmol/L

Hepatic:

• Aspartate transaminase (AST) ≤ 5.0 x ULN
• Alanine transaminase (ALT) ≤ 5.0 x ULN
• Total bilirubin < 1.5 x ULN

Renal:

• Calculated creatinine clearance (using Cockcroft-Gault formula) > 45 cc/min

Cardiovascular:

• No history of Torsades de Pointes, ventricular tachycardia, ventricular fibrillation or ventricular flutter

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • Medical & Surgical Specialists, LLC
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Cancer Care Center of Southern Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
    • Lafayette, Indiana, United States, 47904
      • Arnett Cancer Care
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Ireland Cancer Center - University Hospitals of Cleveland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological or cytological confirmed adenocarcinoma of the breast with locally advanced or metastatic disease.
• Must be able and willing to enroll in the companion study entitled "Predicting Response and Toxicity in Patients Receiving Lonafarnib for Breast Cancer: A Multicenter Genomic, Proteomic and Pharmacogenomic Correlative Study: Hoosier Oncology Group COE-03."
• Must have measurable disease per RECIST as evaluated by imaging within 28 days prior to registration for protocol therapy.
• Must be willing to not drink grapefruit juice for the duration of lonafarnib therapy.
• Previously radiated area(s) must not be the only site of disease for study entry.
• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time of consent until at least 90 days following completion of study treatment.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy. Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
• Females must not be breastfeeding.
• Written informed consent and HIPAA authorization for release of personal health information.
• Age > 18 years

Exclusion Criteria:

• No history or radiologic evidence of CNS metastases including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement (head CT or MRI must be obtained within 42 days prior to registration for protocol therapy).
• No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
• No history of Torsades de Pointes, ventricular tachycardia, ventricular fibrillation or ventricular flutter.
• No history of syncope.
• No history of seizures.
• No prolonged QTc interval > 450msec on pre-entry electrocardiogram obtained within 28 days prior to registration for protocol therapy.
• No history of hypokalemia that cannot be corrected prior to registration for protocol therapy.
• No radiation within 14 days prior to registration for protocol therapy. Patients must have recovered from the acute toxic effects prior to registration for protocol therapy.
• No prior chemotherapy within 21 days prior to registration for protocol therapy.
• No clinically active serious infections as judged by the treating investigator (CTC v3, > Grade 2) including known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Following concomitant medications must be discontinued 7 days prior to registration for protocol therapy and for the duration of lonafarnib therapy: bisphosphonates, including but not limited to etidronate (Didronel), pamidronate (Aredia), alendronate (Fosamax), risedronate (Actonel), zoledronate (Zometa or Reclast), ibandronate (Boniva), ethinylestradiol, gestodene, itraconazole, ketoconazole, cimetidine, erythromycin, carbamazepine, high dose chronic steroids, phenobarbital, phenytoin, rifampin (rifampicin), sulfinpyrazone

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lonafarnib; All registered patients will be treated with Lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator's discretion.	Drug: Lonafarnib; All registered patients will be treated with Lonafarnib 200 mg PO BID daily on days 1-21 of every 21-day cycle until progression of disease, unacceptable toxicity, or investigator's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	To determine progression-free survival of lonafarnib in patients with metastatic breast cancer.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	To determine overall response rate.	18 months
Toxicity Profile of Lonafarib	To determine the toxicity profile of lonafarnib in this patient population.	18 months
Clinical Benefit Response Rate (Complete Response (CR)+Partial Response(PR)+Stable Disease(SD) > 180 Day Duration).		18 months

Collaborators and Investigators

• Sponsor: George Sledge
• Collaborators: Hoosier Cancer Research Network; Schering-Plough
• Investigators: Principal Investigator: George Sledge, M.D., Hoosier Cancer Research Network; Principal Investigator: Brian Leland-Jones, M.D., Hoosier Cancer Research Network

Publications and helpful links

Helpful Links

• Hoosier Oncology Group Homepage
• ASCO Poster

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: October 14, 2008
• First Submitted That Met QC Criteria: October 14, 2008
• First Posted (Estimate): October 16, 2008

Study Record Updates

• Last Update Posted (Estimate): February 18, 2016
• Last Update Submitted That Met QC Criteria: January 21, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lonafarnib
• Other Study ID Numbers: HOG BRE07-126