A Randomized Phase III Trial of the value of early local therapy for the intact primary tumor in patients with metastatic breast cancer

Summary

Protocol e2108 is designed to examine the value of early local therapy for the primary tumor in arm B versus standard of care in arm a. Laboratory measurements that involve comparison of pre and post local therapy values can therefore only be performed in arm B. Howevere, teh Circulating Tumor Cell (CTC) burden prior to primary site local therapy may be substantially reduced by the preceding induction systemic therapy. Statistical testing of CTC values pre and post local therapy in arm B may therefore not be feasible. a more robust comparison would be one performed at six months following randomization, where local therapy would be completed in arm B and the CTC burden would represent the cumulative effects of local and systemic therapy (arm B) versus systemic therapy alone (arm a).

Participant Eligibility

Registration (STEP 1)
1. Patients (male or female) 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.

2. Patients should have at least one site of distant metastatic disease. If only a single
metastatic lesion is present, biopsy is mandatory. See Section 4.

3. Radiology reports documenting status of disease prior to initiation of systemic
therapy must be available. Scans must have been completed within 4 weeks prior to
start of systemic therapy.

Baseline studies must be performed 8 weeks prior to the start of systemic therapy. 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 disease must be available.


4. If patient has only one site of metastatic disease, 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.



5. Patients may have had prior non-invasive (DCIS) cancer if there has been no recurrence.

6. 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.

7. Women of childbearing potential and sexually active males must be strongly advised
to use an accepted and effective method of contraception.
8. Patients with CNS metastases are eligible (as long as projected survival is > 6
months).

3.2 Randomization (STEP 2)
1. Date of randomization must be within 20 weeks of initiation of optimal systemic therapy.
2. Patients must have completed at least 16 weeks of optimal systemic therapy
(appropriate to the tumor biological profile and the patient[Single Quote]s age and menopausal
status), during which no more than 2 weeks of unscheduled dose interruption
occurred for any reason. Rest weeks that are part of the schedule for treatment
administration are included when calculating the duration of therapy.
3. Documentation regarding the details of administration of all systemic chemotherapy
must be available.
4. Patients must be judged to be candidates for complete resection with free margins
followed by radiation therapy.
5. Local disease at the primary site must be asymptomatic (no skin nodules or skin
invasion, no ulceration, and no chest wall fixation).
6. Patients must have adequate organ function < 2 weeks prior to randomization, as
measured by:
a. Absolute neutrophil count > 1000/mm3

b. Platelet count > 100,000/mm3

c. Total bilirubin < 1.5 mg/dL

d. AST < 2 X upper limit of normal

e. Serum creatinine < 1.5 mg/dL

If systemic therapy is changed for reasons other than progression of disease (e.g. from chemotherapy to endocrine therapy), the patient remains eligible.