Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
| Phase | Type | Status | Age | Sponsor | Protocol IDs |
|---|---|---|---|---|---|
| Phase III, Phase II | Treatment | Completed | any age | NCI | E-1193 NCCTG-923252, SWOG-9332, E-10292, E1193 |
Objectives
I. Compare the objective response rate and time to progression of patients with metastatic breast cancer, who have not had prior therapy for advanced disease following treatment with doxorubicin (DOX) vs. paclitaxel (TAX) vs. DOX/TAX with granulocyte colony-stimulating factor (G-CSF). II. Compare the toxicity of these 3 regimens. III. Determine by means of a crossover design whether DOX and TAX exhibit cross-resistance. IV. Compare the quality of life of patients who receive DOX vs. TAX vs. TAX/DOX/G-CSF. V. Compare the quality of life of patients who receive DOX vs. TAX as second-line therapy. VI. Evaluate the relation of steady-state TAX levels to therapeutic response and toxicity.
Entry Criteria
Disease Characteristics:
Histologically confirmed adenocarcinoma of the breast that is regionally
progressing or metastatic
Measurable or evaluable disease required as follows (initial measurements
within 2 weeks prior to entry):
Bidimensionally or unidimensionally measurable lesions, including:
Malignant disease measurable in 2 dimensions by ruler or calipers
(metastatic pulmonary nodules, lymph nodes, subcutaneous metastases)
Lesions with sharply defined borders measurable on ultrasound or CT
Mediastinal and hilar lesions on x-ray, provided a pre-involvement chest
x-ray is available
Hepatic metastases readily measurable on CT or MRI
Malignant hepatomegaly with the sum of the measurements of the liver edge
below the costal margin and below the tip of the xiphoid in the
midclavicular line on quiet respiration at least 5 cm
Evaluable lesions evident on clinical or radiologic exam but not measurable
by ruler or calipers, including:
Cytologically positive pleural and peritoneal effusions
Local intracavitary treatment not allowed at beginning of protocol
treatment
Pleural effusions must not have been drained nor be sclerosed
Blastic and mixed blastic/lytic osseous metastases only if accompanied by
either an analgesic requirement or a decrease in performance status and
proven on x-ray
No requirement for radiotherapy during the first two courses of
treatment
Pure osteolytic lesions
Intra-abdominal or pelvic mass visualized on CT
Multinodular or confluent, nonmeasurable lung or skin metastases
Brain metastases must have responded to prior radiotherapy or surgery and
continue to be in response
Other measurable disease required
Hormone receptor status:
Not specified
Prior/Concurrent Therapy:
Biologic therapy:
Not specified
Chemotherapy:
No prior systemic anthracyclines (e.g., doxorubicin), anthracenes (e.g.,
mitoxantrone), paclitaxel, or docetaxel (taxotere)
No prior chemotherapy for overt metastatic disease
At least 6 months since adjuvant chemotherapy or at least 6
months between such therapy and diagnosis of metastatic
disease
Endocrine therapy:
At least 2 weeks since hormonal therapy for advanced disease
Prior adjuvant hormonal therapy allowed
Radiotherapy:
No prior radiotherapy except:
Irradiation of the breast, chest wall, or axilla
Limited-field irradiation of less than 25% of marrow-containing bone
At least 2 weeks since radiotherapy
Surgery:
At least 4 weeks since major surgery and fully recovered
Patient Characteristics:
Age:
Any age
Sex:
Women only
Menopausal status:
Not specified
Performance status:
ECOG 0-2
Life expectancy:
At least 3 months
Hematopoietic:
(obtained within 2 weeks prior to entry)
AGC at least 1,500
Platelets at least 100,000
Hepatic:
(obtained within 2 weeks prior to entry)
Bilirubin no greater than 2 times normal
AST no greater than 2.5 times normal
Renal:
(obtained within 2 weeks prior to entry)
Creatinine no greater than 2 times normal
Cardiovascular:
No history of congestive heart failure
No myocardial infarction within the past 6 months
No history of ischemic heart disease requiring medication
No arrhythmia requiring medication
No requirement for drugs known to alter cardiac conduction:
Digoxin
Propranolol
Calcium channel blockers
No venous thrombotic condition, including:
Deep venous thrombophlebitis
Pulmonary or other thromboembolism
Other:
No history of allergic reaction to drugs using the vehicle
Cremophor (e.g., anesthetics and muscle relaxants)
No active, unresolved infection
At least 7 days since parenteral antibiotics
No second malignancy within 5 years except:
Curatively treated nonmelanomatous skin cancer
Curatively treated in situ cervical cancer
No pregnant women
Adequate contraception required of fertile patients
Participation in a quality-of-life assessment optional
Expected Enrollment
A maximum of 733 patients will be entered over approximately 22 months; 220 evaluable patients will be accrued to Arms A and B. If at least 11 responses are seen in the first 40 patients entered on Arm C (phase II portion of the study), a total of 220 evaluable patients will be enrolled on that arm as well.
Outline
Randomized study. Arm A: Single-Agent Chemotherapy. Doxorubicin, DOX, NSC-123127. Arm B: Single-Agent Chemotherapy. Paclitaxel, TAX, NSC-673089. Arm C: 2-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation. DOX; TAX; with Granulocyte Colony-Stimulating Factor (Amgen), G-CSF, NSC-614629.Published Results
Eton DT, Cella D, Yost KJ, et al.: Minimally important differences on the functional assessment of cancer therapy-breast (FACT-B) scale: results from ECOG study 1193 . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2142, 2003.
Sledge GW, Neuberg D, Bernardo P, et al.: Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 21 (4): 588-92, 2003.[PUBMED Abstract]
Extermann M, Bonetti M, Sledge GW, et al.: MAX2: A convenient index to estimate the average per patient risk of severe toxicity from a chemotherapy regimen. Testing in ECOG studies. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1459, 2002.
Zon R, Neuberg D, Wood WC, et al.: Correlation of plasma VEGF(P-VEGF) with clinical outcome in patients with metastatic breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A712, 185a, 1998.
Neuberg D, Sledge GW, Fetting J, et al.: Changes in quality of life (QOL) during induction therapy in patients enrolled in a randomized trial of adriamycin, taxol, and adriamycin plus taxol in metastatic breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A185, 54a, 1997.
Sledge GW, Neuberg D, Ingle J, et al.: Phase III trial of doxorubicin (A) vs. paclitaxel (T) vs. doxorubicin + paclitaxel (A+T) as first-line therapy for metastatic breast cancer (MBC). [Abstract] Proceedings of the American Society of Clinical Oncology 16: A-2, 1a, 1997.
Stender M, Neuberg D, Wood WC, et al.: Correlation of circulating c-erb B-2 extracelluar domain (her-2) with clinical outcome in patients with metastatic breast cancer (MBC). [Abstract] Proceedings of the American Society of Clinical Oncology 16: A541, 154a, 1997.
Related PublicationsExtermann M, Bonetti M, Sledge GW, et al.: MAX2--a convenient index to estimate the average per patient risk for chemotherapy toxicity; validation in ECOG trials. Eur J Cancer 40 (8): 1193-8, 2004.[PUBMED Abstract]
Extermann M, Bonetti M, Sledge GW, et al.: MAX2: A convenient index to estimate the average per patient risk of severe toxicity from a chemotherapy regimen. Testing in ECOG studies. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1459, 2002.
Trial Lead Organizations
Eastern Cooperative Oncology Group
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| George Sledge, MD, Protocol chair | |
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North Central Cancer Treatment Group
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| James Ingle, MD, Protocol chair | |
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Southwest Oncology Group
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| Silvana Martino, DO, Protocol chair | |
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Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.
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