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

Alternate Title

Neoadjuvant Tipifarnib, Docetaxel, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIA or Stage IIIB Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 and over NCI MAYO-MC0131 NCI-5599, 5599, NCT00070252, WSU-C-2679

Objectives

Phase Ib

1. Determine the maximum tolerated dose and recommended dose of capecitabine in combination with docetaxel and tipifarnib in patients with locally advanced or metastatic solid tumors.

Phase II

Primary

1. Determine the complete pathological and clinical response rate in patients with stage IIIA or IIIB breast cancer treated with this regimen.

Secondary

1. Determine the toxicity of this regimen in these patients.
2. Determine disease-free and overall survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

Phase Ib

• Histologically or cytologically confirmed solid tumor
  • Locally advanced or metastatic



• No known standard therapy that is potentially curative or definitely capable of extending life expectancy



• No history of metastatic brain disease within the past 6 months
  • Treated metastatic brain disease is allowed provided disease has been stable for more than 6 months and does not require concurrent steroids or anti-seizure medication

Phase II

• Histologically confirmed breast cancer
  • Stage IIIA or stage IIIB, including ipsilateral palpable supraclavicular lymph node(s) without other distant metastasis
  • Invasive disease confirmed by 1 of the following*:
    • Incisional biopsy
    • Punch biopsy (applicable for clinical T4b tumors)
    • Core needle (cutting needle) biopsies

     [Note: *No positive cytology by fine-needle aspirate only]




• No distant metastatic disease



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• Phase Ib only:
  • More than 4 weeks since prior immunotherapy
  • More than 4 weeks since prior biologic therapy
  • No concurrent immunotherapy
• Phase Ib and II:
  • No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy

• Phase Ib only:
  • More than 1 year since prior adjuvant docetaxel before metastatic relapse
  • More than 4 weeks since prior chemotherapy and recovered
  • No prior capecitabine AND docetaxel (in combination or as single agents)
    • Prior capecitabine OR docetaxel allowed
  • No other concurrent chemotherapy
• Phase II only:
  • No prior cytotoxic chemotherapy for breast cancer

Endocrine therapy

• Not specified

Radiotherapy

• Phase Ib only:
  • More than 3 weeks since prior radiotherapy
  • No prior radiotherapy to more than 25% of bone marrow
  • No concurrent radiotherapy
• Phase II only:
  • No prior radiotherapy for breast cancer

Surgery

• Phase Ib only:
  • More than 4 weeks since prior major surgery
• Phase II only:
  • No prior surgery (other than core or incisional biopsy for diagnostic purposes) for breast cancer

Other

• Phase Ib only:
  • No other ancillary investigational therapy
• Phase Ib and II:
  • No concurrent sorivudine or brivudine

Patient Characteristics:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 2,000/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 10.0 g/dL

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN
• AST no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.25 times ULN

  OR

• Creatinine clearance at least 50 mL/min

Cardiovascular

• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring antibiotics
• No diabetes
• No symptomatic neurologic condition
• No other uncontrolled serious medical condition
• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No history of hypersensitivity to intravenous paclitaxel or other medication containing Cremophor EL or polysorbate 80 as a carrier (phase Ib)

Expected Enrollment

A total of 24-53 patients (9-18 for phase Ib and 15-35 for phase II) will be accrued for this study within 14-35 months.

Outcomes

Maximum tolerated dose as measured by clinical evaluation and laboratory tests (Phase I)
Complete pathological response rate as measured by the disappearance of all invasive cancer in the primary tumor and lymph node at post-neoadjuvant chemotherapy and surgery (Phase II)

Toxicity as measured from start of treatment up to 30 days after completion of study treatment
Clinical response rate measured at time of post-neoadjuvant chemotherapy and surgery
Overall survival and disease-free survival as measured by radiological evaluation from registration until disease progression or death

Outline

This is a multicenter, dose-escalation study of capecitabine. Patients in phase II are stratified according to type of breast cancer (inflammatory vs noninflammatory).

• Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.




• Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine.

Patients in phase Ib are followed at 3 months. Patients in phase II are followed every 4 months for up to 5 years.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Philip Philip, MD, PhD, FRCP, Protocol chair		Ph: 313-576-8728; 800-527-6266 Email: philipp@karmanos.org

Registry Information
Official Title		Phase Ib/II Neoadjuvant Trial Of The Farnesyltransferase Inhibitor, R115777 With Docetaxel And Capecitabine For Patients With Stage IIIA Or IIIB Breast Cancer
Trial Start Date		2003-09-18
Registered in ClinicalTrials.gov		NCT00070252
Date Submitted to PDQ		2003-08-21
Information Last Verified		2005-12-12
NCI Grant/Contract Number		P30-CA15083, N01-CM17104

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