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

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070252

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Breast Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: capecitabine Drug: docetaxel Drug: tipifarnib Procedure: neoadjuvant therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Docetaxel Capecitabine R 115777 Tipifarnib

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated dose as measured by clinical evaluation and laboratory tests (Phase I) [ Designated as safety issue: Yes ]
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) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity as measured from start of treatment up to 30 days after completion of study treatment [ Designated as safety issue: Yes ]
Clinical response rate measured at time of post-neoadjuvant chemotherapy and surgery [ Designated as safety issue: No ]
Overall survival and disease-free survival as measured by radiological evaluation from registration until disease progression or death [ Designated as safety issue: No ]

Study Start Date:	September 2003
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Phase Ib

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
- Determine the complete pathological and clinical response rate in patients with stage IIIA or IIIB breast cancer treated with this regimen.
Secondary
- Determine the toxicity of this regimen in these patients.
- 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

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

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

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

Contacts and Locations

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

Locations

United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259
United States, District of Columbia
Howard University Cancer Center at Howard University Hospital
Washington, District of Columbia, United States, 20060
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Philip A. Philip, MD, PhD, FRCP

Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00070252 History of Changes
Other Study ID Numbers:	CDR0000331694, MAYO-MC0131, NCI-5599, WSU-C-2679
Study First Received:	October 3, 2003
Last Updated:	June 26, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

inflammatory breast cancer
male breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Tipifarnib
Capecitabine
Fluorouracil

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012