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A Phase I/II Trial of Docetaxel Followed by Infusional Flavopiridol Over 72 Hours in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase I/II Trial of Docetaxel Followed by Infusional Flavopiridol Over 72 Hours in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer


- Determine the maximum tolerated dose of docetaxel and flavopiridol in patients with
previously treated locally advanced or metastatic breast cancer.

- Determine the dose-limiting toxicity, toxicity profile, and pharmacokinetics of this
regimen in these patients.

- Determine the activity of this regimen in these patients.

- Determine the objective response rate in patients treated with this regimen.

- Determine immune dysfunction produced by this regimen as measured by lymphocyte
subpopulations, including T-cell activation/memory subsets and natural killer
cell/lymphokine-activated killer cell functional subsets in these patients.

- Determine the ability of positron emission tomography scanning to predict response in
patients treated with this regimen.

- Determine the response duration, time to treatment failure, and overall survival of
patients treated with this regimen.

- Determine the quality of life of patients treated with this regimen.

- Determine whether this regimen is associated with the development of a prothrombotic
state in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive docetaxel IV over 1 hour on day 1 followed by flavopiridol IV over 1 hour
or IV continuously on days 2-4. Treatment repeats every 3 weeks in the absence of disease
progression or unacceptable toxicity.

Sequential dose escalation of docetaxel is preceded or followed by sequential dose
escalation of flavopiridol. Cohorts of 3-6 patients receive escalating doses of docetaxel
preceded or followed by escalating doses of flavopiridol until the maximum tolerated dose
(MTD) of the combination is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 22
additional patients are accrued to receive flavopiridol and docetaxel at the recommended
phase II dose.

Quality of life is assessed at baseline, every 3 courses during study, and then at
completion of study.

PROJECTED ACCRUAL: A total of 49 patients (27 for phase I and 22 for phase II) will be
accrued for this study within 2 years.

Inclusion Criteria


- Histologically confirmed stage III or IV adenocarcinoma of the breast

- Phase I:

- Evaluable disease allowed

- Phase II:

- At least 1 site of measurable disease

- No bone metastasis as only site of disease

- No carcinomatous meningitis or brain metastases

- Hormone receptor status:

- Not specified



- 18 and over


- Male or female

Menopausal status:

- Not specified

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified


- Granulocyte count at least 1,500/mm^3

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

- No active coagulopathy requiring therapeutic anticoagulation


- Bilirubin no greater than upper limit of normal (ULN)

- SGOT no greater than 1.5 times ULN

- Alkaline phosphatase no greater than 2.5 times ULN

- No Gilbert's disease


- Creatinine no greater than 1.5 mg/dL


- Left ventricular ejection fraction at least 50% without clinical signs or symptoms of
heart failure

- No uncontrolled hypertension (sustained systolic blood pressure (BP) greater than 180
mm Hg or diastolic BP greater than 100 mm Hg)

- No uncontrolled cardiac arrhythmia

- No myocardial infarction within the past year

- No significant ischemia or valvular heart disease


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No medical or psychiatric condition that would increase risk

- No other malignancy within the past 5 years except carcinoma in situ of the cervix or
nonmelanomatous skin cancer

- No grade 2 or greater peripheral neuropathy

- No diabetes mellitus with a fasting blood sugar greater than 200 mg/dL

- No active unresolved infection

- No serious concurrent medical illness

- No history of hypersensitivity reaction to products containing polysorbate 80 (Tween


Biologic therapy:

- Not specified


- No prior flavopiridol

- Prior adjuvant chemotherapy for advanced disease allowed if within 6 months of
diagnosis of metastatic disease

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea or 8 weeks for
UCN-01) and recovered

- Phase I:

- Any number of prior chemotherapy regimens for metastatic carcinoma of the breast

- Phase II:

- No more than 2 prior chemotherapy regimens for metastatic carcinoma of the

Endocrine therapy:

- Prior hormonal therapy in the metastatic or adjuvant setting allowed

- At least 2 weeks since prior hormonal therapy and no evidence of disease improvement
by radiography after therapy

- Concurrent corticosteroids allowed if for study premedication or hypersensitivity
reactions/adverse events


- No concurrent radiotherapy


- Not specified


- No other concurrent antineoplastic therapies

- No other concurrent investigational drugs

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Antoinette R. Tan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

October 2000

Completion Date:

March 2003

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • stage IIIA breast cancer
  • recurrent breast cancer
  • stage IIIB breast cancer
  • male breast cancer
  • Breast Neoplasms



Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182