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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00070252
First received: October 3, 2003
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

Phase I/II trial to study the effectiveness of neoadjuvant tipifarnib combined with docetaxel and capecitabine in treating patients who have locally advanced or metastatic solid tumors or stage IIIA or stage IIIB breast cancer. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy, such as docetaxel and capecitabine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining tipifarnib with docetaxel and capecitabine may kill more tumor cells.


Condition Intervention Phase
Inflammatory Breast Cancer
Male Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: tipifarnib
Drug: capecitabine
Drug: docetaxel
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Pathologic complete response rate (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated by the number of patients with a complete pathologic response divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true pathologic complete response probability will be calculated according to the approach of Duffy and Santner.


Secondary Outcome Measures:
  • Clinical tumor response (complete response [CR] or partial response [PR]) (Phase I) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Clinical responses will be summarized by simple descriptive summary statistics.

  • Toxicity as assessed by the National Cancer Institute (NCI) CTCAE version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.


Enrollment: 53
Study Start Date: September 2003
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tipifarnib, capecitabine, docetaxel)

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.

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.

Drug: tipifarnib
Given orally (PO)
Other Names:
  • R115777
  • Zarnestra
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070252

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, District of Columbia
Howard University Cancer Center CCOP
Washington, District of Columbia, United States, 20060
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Medical School
Milwaukee, Wisconsin, United States, 53201
Sponsors and Collaborators
Investigators
Principal Investigator: Philip Philip Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070252     History of Changes
Other Study ID Numbers: NCI-2012-01442, MC0131, WSU-C-2679, MAYO-MC0131, NCI-5599, CDR0000331694, N01CM62205
Study First Received: October 3, 2003
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Inflammatory Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Docetaxel
Fluorouracil
Tipifarnib
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014