Lonafarnib in Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00773474
• Other study ID #: HOG BRE07-126
• Status: Terminated
• Phase: Phase 2
• First received: October 14, 2008
• Last updated: January 21, 2016
• Start date: October 2008
• Est. completion date: November 2010

Study information

• Verified date: January 2016
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

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.

Locations

Country	Name	City	State
United States	Cancer Care Center of Southern Indiana	Bloomington	Indiana
United States	Ireland Cancer Center - University Hospitals of Cleveland	Cleveland	Ohio
United States	Medical & Surgical Specialists, LLC	Galesburg	Illinois
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Arnett Cancer Care	Lafayette	Indiana
United States	Horizon Oncology Center	Lafayette	Indiana

Sponsors (3)

Lead Sponsor	Collaborator
George Sledge	Hoosier Cancer Research Network, Schering-Plough

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	To determine progression-free survival of lonafarnib in patients with metastatic breast cancer.	18 months	No
Secondary	Overall Response Rate	To determine overall response rate.	18 months	No
Secondary	Toxicity Profile of Lonafarib	To determine the toxicity profile of lonafarnib in this patient population.	18 months	Yes
Secondary	Clinical Benefit Response Rate (Complete Response (CR)+Partial Response(PR)+Stable Disease(SD) > 180 Day Duration).		18 months	No

External Links

•   ASCO Poster
•   Hoosier Oncology Group Homepage