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Phase Ib/II Neoadjuvant Trial of the Farnesyltransferase Inhibitor, R115777 With Docetaxel and Capecitabine for Patients With Stage IIIA or IIIB Breast Cancer


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Inflammatory Breast Cancer, Male Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase Ib/II Neoadjuvant Trial of the Farnesyltransferase Inhibitor, R115777 With Docetaxel and Capecitabine for Patients With Stage IIIA or IIIB Breast Cancer


PRIMARY OBJECTIVES:

I. 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 Ib) II. Determine the complete pathological and clinical response rate in patients
with stage IIIA or IIIB breast cancer treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

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

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.

PROJECTED ACCRUAL: 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.


Inclusion Criteria:



- 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

- 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

- No distant metastatic disease

- Hormone receptor status:

- Not specified

- Male or female

- Performance status - ECOG 0-1

- Absolute neutrophil count at least 2,000/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 10.0 g/dL

- 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

- Creatinine no greater than 1.25 times ULN

- Creatinine clearance at least 50 mL/min

- No cardiac arrhythmia

- 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)

- 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)

- 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

- 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

- 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

- Phase Ib only:

- No other ancillary investigational therapy

- Phase Ib and II:

- No concurrent sorivudine or brivudine

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I)

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Philip Philip

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01442

NCT ID:

NCT00070252

Start Date:

September 2003

Completion Date:

Related Keywords:

  • Inflammatory Breast Cancer
  • Male Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Breast Neoplasms
  • Breast Neoplasms, Male
  • Inflammatory Breast Neoplasms

Name

Location

Mayo ClinicRochester, Minnesota  55905
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Washington University School of MedicineSaint Louis, Missouri  63110
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224
University of Wisconsin Medical SchoolMadison, Wisconsin  53792-0001
Howard University Cancer Center CCOPWashington, District of Columbia  20060