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Phase II/III Randomized Trial of DOX vs TAX vs DOX/TAX/G-CSF in Patients with Metastatic Breast Cancer
Basic Trial Information
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
North Central Cancer Treatment Group
Southwest Oncology Group
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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