Clinical trial NCT00004092: Combination Chemotherapy in Treating Patients With High-Risk Breast Cancer
Official title: Randomized Phase II Study of Adriamycin/Cytoxan/Taxol (ACT) vs. Cytoxan, Thiotepa, Carboplatin (STAMP V) in Patients With High-Risk Primary Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 72
Sex: ALL
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying two different regimens of combination chemotherapy and comparing them to see how well they work in treating patients with high-risk primary stage II or stage III breast cancer.

Detailed description: OBJECTIVES:

* Compare the toxic effects of doxorubicin, cyclophosphamide, and paclitaxel vs cyclophosphamide, thiotepa, and carboplatin in patients with high-risk primary breast cancer. (Arm I closed to accural as of 4/6/2006.)
* Compare the efficacies of these regimens followed by peripheral blood stem cell rescue in these patients.
* Determine the efficacy of a bisphosphonate to prevent relapse/metastasis after high-dose chemotherapy in these patients.

OUTLINE: This is a randomized study. Patients are stratified by stage of disease.

Peripheral blood stem cells (PBSC) are collected after mobilization with filgrastim (G-CSF), administered subcutaneously or IV, twice daily beginning 3 days before collection and continuing until collection is complete.

All patients receive conventional-dose adjuvant chemotherapy, probably comprising doxorubicin IV, cyclophosphamide IV, and fluorouracil IV over 1 hour on days 1, 22, 43, and 64. Patients are then randomized to receive 1 of 2 treatment arms of high-dose chemotherapy. (Arm I closed to accrual as of 4/6/2006.)

* Arm I (ACT) (closed to accrual as of 4/6/2006): Patients receive doxorubicin IV over 24 hours on days -9 to -6, cyclophosphamide IV over 2 hours on day -5, and paclitaxel IV over 24 hours on day -2. PBSC are reinfused on days -2 and 0. G-CSF is administered beginning on day 0 and continuing until blood counts recover.
* Arm II (STAMP V): Patients receive cyclophosphamide IV, carboplatin IV, and thiotepa IV over 24 hours on days -7 to -4. PBSC are reinfused and G-CSF is administered as in arm I.

Within 4-6 weeks of day 0 of high-dose chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen twice daily for 5 years. Patients are also randomized to receive a bisphosphonate comprising pamidronate IV every 4 weeks for 2 years.

Quality of life is assessed before therapy, at 30 days after high-dose chemotherapy, and at 6 and 12 months.

Patients are followed every 3 months for 1 year and then every 6 months for at least 10 years.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven high-risk primary breast cancer with less than 60% chance of progression-free survival of 3 years from diagnosis

  * Stage II with at least 10 positive axillary nodes OR
  * Stage IIIA or IIIB
* No histologically proven bone marrow metastasis
* No CNS metastasis
* Hormone receptor status:

  * Hormone receptor status known

PATIENT CHARACTERISTICS:

Age:

* Physiological age 60 or under

Menopausal status:

* Not specified

Performance status:

* Karnofsky 80-100%

Life expectancy:

* See Disease Characteristics

Hematopoietic:

* Neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* SGOT or SGPT no greater than 2 times upper limit of normal
* Hepatitis B antigen negative

Renal:

* Creatinine no greater than 1.2 mg/dL
* Creatinine clearance at least 70 mL/min
* No prior hemorrhagic cystitis

Cardiovascular:

* Ejection fraction at least 55% by MUGA
* No prior significant valvular heart disease or arrhythmia

Pulmonary:

* FEV_1 at least 60% of predicted
* pO_2 at least 85 mm Hg on room air
* pCO_2 at least 43 mm Hg on room air
* DLCO at least 60% lower limit of predicted

Other:

* No other prior malignancy except squamous cell or basal cell skin cancer or stage I or carcinoma in situ of the cervix
* No CNS dysfunction that would preclude compliance
* HIV negative
* No sensitivity to E. coli-derived products
* Not pregnant
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* At least 4 weeks since prior chemotherapy
* No prior doxorubicin of total dose exceeding 240 mg/m\^2
* No prior paclitaxel of total dose of at least 750 mg/m\^2
* No more than 12 months since prior conventional-dose adjuvant chemotherapy

Endocrine therapy:

* At least 4 weeks since prior hormonal therapy

Radiotherapy:

* At least 4 weeks since prior radiotherapy
* No prior radiation to the left chest wall

Surgery:

* Not specified

Primary outcomes:
measure: Five-Year Relapse-free Survival
timeFrame: Five years
Secondary outcomes:
measure: Five-Year Overall Survival
timeFrame: Five Years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: George Somlo, MD
role: PRINCIPAL_INVESTIGATOR
References: