Early Surgery or Standard Palliative Therapy in Treating Patients with Stage IV Breast Cancer
Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Treatment||18 and over||E2108|
NCI-2011-02645, CDR0000688097, ECOG-E2108, NCT01242800
This randomized phase III trial studies early surgery to see how well it works compared to standard palliative therapy in treating patients with stage IV breast cancer. Early surgery may have fewer side effects and improve recovery. Palliative surgery or radiation therapy may help patients with advanced breast cancer live more comfortably. It is not yet known whether early surgery is more effective than palliative therapy for advanced breast cancer.
Further Study Information
I. To evaluate whether early local therapy of intact primary disease in patients with stage IV breast cancer whose disease does not progress during initial optimal systemic therapy, will result in prolonged survival, compared to women who receive local therapy for palliation only.
I. To compare the time to uncontrolled chest wall disease between patients who receive early local therapy versus patients who receive palliative local therapy.
II. To determine whether there is a difference in health related quality of life (HRQL) between patients who receive early local therapy and those who receive palliative local therapy.
III. To determine whether the absolute value of the circulating tumor cells (CTC) burden at six months following randomization will be lower in Arm B than Arm A and whether this value is inversely related to survival.
IV. To collect tumor and blood specimens for future exploration of the biological interactions between the primary tumor and metastatic lesions and the effect of primary tumor resection.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive standard palliative therapy, if needed, to address symptoms such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a combination of both.
ARM B: Patients undergo surgery comprising breast-conserving therapy (BCT) or total mastectomy according to patient and treating physician preference no later than 10 weeks after randomization. Free surgical margins must be achieved with re-excision or mastectomy for patients undergoing BCT. After completion of BCT, patients undergo radiotherapy once a day, 5 days per week. Patients who had mastectomy undergo radiotherapy at the discretion of treating physician.
After completion of study therapy, patients are followed up periodically for 5 years.
Patients with a history of other primary cancers are eligible if the pathology report confirming the diagnosis of primary breast cancer is available and the other primary cancer was curatively treated with a 5-year disease-free interval
Patients with non-melanoma skin cancer are eligible; however, patients with squamous cell carcinoma of other sites (except in-situ cervix) are not eligible
Patients must have completed at least 16 weeks of optimal systemic therapy (appropriate to the tumor biological profile and the patient’s age and menopausal status)
NOTE: The patient will be considered eligible if the last day of the treatment cycle meets the 16 weeks criteria
If systemic therapy is discontinued for toxicity, there is no distant progression and at least 12 weeks of therapy have been delivered, then the patient remains eligible; if systemic therapy is changed for reasons other than progression of disease (e.g. from chemotherapy to endocrine therapy), the patient remains eligible
Documentation regarding the details of administration of all systemic chemotherapy must be available
If patient has only one metastatic lesion/focus, this must be proven by biopsy and the pathology report confirming the diagnosis of primary breast cancer, as well as the metastatic site, must be available
Patients may have had prior non-invasive (ductal carcinoma in situ [DCIS]) cancer if there has been no recurrence; prior ipsilateral invasive cancer also allowed if more than 5 years previous
Patients should have at least one organ system involved with distant metastatic disease; if only a single metastatic lesion is present, biopsy is mandatory
Patients must have an intact primary (not recurrent) invasive carcinoma of the breast; biopsy confirmation of the primary tumor should be by needle biopsy (preferred); incisional surgical biopsy is allowed as long as there is residual palpable or imageable tumor in the breast
Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy
Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
Patients with central nervous system (CNS) metastases are eligible (as long as projected survival is > 6 months)
Patients who require radiotherapy to distant metastases during induction systemic therapy are eligible
Local disease at the primary site must be asymptomatic
Patients must have adequate organ function to undergo local therapy 4 weeks +/ - 2 weeks prior to randomization per investigator discretion and institutional guidelines
Date of randomization must be within 32 weeks of initiation of optimal systemic therapy
Patients must be judged to be candidates for complete resection with free margins followed by radiation therapy (if radiation therapy is indicated)
Patients with synchronous contralateral invasive breast cancer are excluded
If palliative radiation to non-breast sites is required prior to initiation of systemic therapy, scans may be completed within 8 weeks prior to or 4 weeks following the start of radiation therapy
Patients must not have experienced distant disease progression since the start of systemic therapy, as evidenced by clinical and radiographic documentation of disease status before treatment and within 6 weeks prior to randomization, including:
No new sites of disease
No enlargement of existing sites by 20% or more in longest diameter
No symptomatic deterioration
Imaging at step 2 should preferably be the same as at step 1 (baseline); it must address all previous sites of disease and all clinical signs and symptoms; if all step 1 imaging tests cannot be repeated, the reason should be documented (e.g. declined by insurance); step 2 imaging must evaluate all known sites of disease and address all signs/symptoms present at step 2
Baseline studies must be performed 8 weeks prior to the start of systemic therapy, and must document the extent of disease in the breast; the specifics of this are at physician discretion, but must address clinical signs and symptoms; if pre-therapy scans were not performed, scans performed within the first 4 weeks of systemic therapy, but prior to registration, will be accepted; radiology reports documenting status of disease must be available
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
ECOG-ACRIN Cancer Research Group
- National Cancer Institute
Colorado Cancer Research Program CCOP
Illinois CancerCare-Galesburg Cottage Plaza Office
Nguyet Anh Le-Lindqwister
Nguyet Anh Le-Lindqwister
Northern Indiana Cancer Research Consortium CCOP
Jose A. Bufill
Jose A. Bufill
Montana Cancer Consortium CCOP
Benjamin T. Marchello
Benjamin T. Marchello
Missouri Valley Cancer Consortium
Gamini S. Soori
Gamini S. Soori
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01242800
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.