Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Capecitabine and Tipifarnib in Treating Women With Taxane-Resistant Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Over 18	NCI	ECOG-E1103 E1103, NCT00077363, NCCTG-E1103

Objectives

Primary

1. Determine the response rate in women with taxane-resistant metastatic breast cancer treated with capecitabine and tipifarnib.

Secondary

1. Determine the toxicity of this regimen in these patients.
2. Determine the progression-free survival, time to treatment failure, and overall survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the breast
  • Metastatic disease



• At least 1 objective measurable disease parameter
  • No prior radiotherapy to only site of measurable disease



• Must have received prior anthracycline therapy (e.g., doxorubicin or epirubicin) in the adjuvant/neoadjuvant setting and/or for metastatic disease



• Must have received prior taxane therapy (e.g., paclitaxel or docetaxel) for metastatic disease OR relapsed while receiving adjuvant taxane therapy



• Progressive disease during or within 30 days after receiving prior taxane therapy



• No prior or concurrent brain metastases



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior capecitabine for metastatic disease
• No prior fluorouracil for metastatic disease

Endocrine therapy

• At least 1 week since prior hormonal therapy in the metastatic or adjuvant/neoadjuvant setting

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• Prior radiotherapy to the conserved breast, to the postmastectomy chest wall, or to a limited field involving less than 25% of marrow-containing bone allowed
• No other prior radiotherapy
• No concurrent radiotherapy

Surgery

• No prior organ allograft

Other

• At least 4 weeks since prior cytotoxic drugs
• No prior tipifarnib
• No other prior farnesyl transferase inhibitors
• No prior immunosuppressive therapy
• No more than 3 prior cytotoxic regimens for metastatic disease
• No concurrent enzyme-inducing anticonvulsant medications (e.g., phenobarbital or phenytoin)
• No concurrent warfarin adjusted to an elevated INR
  • Concurrent prophylactic low-dose warfarin (e.g., 1 mg daily) allowed provided PT and INR are normal

Patient Characteristics:

Age

• Over 18

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count > 1,500/mm³
• Platelet count > 100,000/mm³

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (5 times ULN if there is liver involvement by tumor)

Renal

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic cardiovascular disease

Gastrointestinal

• No chronic nausea and vomiting
• No complete or partial bowel obstruction
• No dysphagia or odynophagia with inability to swallow pills

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No greater than grade 1 neuropathy
• No ongoing or active infection
• No other chronic medical or psychiatric illness that would preclude study participation or compliance
• No other concurrent uncontrolled illness

Expected Enrollment

A total of 70 patients will be accrued for this study within 7 months.

Outcomes

Objective response rate (partial and complete response)

Progression-free survival
Time to treatment failure
Overall survival
Toxicity

Outline

This is a multicenter study.

Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 4 additional courses beyond documentation of CR.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Wang M, Gradishar WJ, Sparano JA, et al.: A phase II trial of capecitabine (C) in combination with the farnesyltransferase (FT) inhibitor (FTI), tipifarnib (T), in patients (pt) with metastatic breast cancer (MBC): ECOG trial 1103. [Abstract] J Clin Oncol 25 (Suppl 18): A-1036, 2007.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

William Gradishar, MD, Protocol chair		Ph: 312-695-4125 Email: w-gradishar@northwestern.edu
Joseph Sparano, MD, Protocol co-chair		Ph: 718-904-2555 Email: jsparano@montefiore.org

North Central Cancer Treatment Group

Edith Perez, MD, Protocol chair		Ph: 507-284-1159 Email: perez.edith@mayo.edu

Registry Information
Official Title		A Phase II Trial Of Capecitabine In Combination With The Farnesyltransferase Inhibitor, R115777 (Tipifarnib and /or Zarnestra) In Patients With Metastatic Breast Cancer
Trial Start Date		2004-05-19
Registered in ClinicalTrials.gov		NCT00077363
Date Submitted to PDQ		2003-12-22
Information Last Verified		2006-04-19
NCI Grant/Contract Number		CA21115

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