In This SectionTexas Health Research & Education Institute
Disease or Condition
ADJUVANT CLODRONATE THERAPY VS PLACEBO IN EARLY-STAGE BREAST CANCER
A CLINICAL TRIAL COMPARING ADJUVANT CLODRONATE THERAPY VS PLACEBO IN EARLY-STAGE BREAST CANCER PATIENTS RECEIVING SYSTEMIC CHEMOTHERAPY AND/OR TOMOXIFEN OR NO THERAPY.
The patient must consent to be in the study and must have signed an approved consent form conforming with federal and institutional guidelines.
The patient must have a life expectancy of at least 10 years, excluding her diagnosis of breast cancer. (Comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer.)
The interval between the last surgery for breast cancer treatment (lumpectomy, mastectomy, sentinel node biopsy, axillary dissection, or re-excision of
lumpectomy margins) and randomization must be less than or equal to 84 days.
Patients must have undergone either a total mastectomy or a lumpectomy with either an axillary dissection or sentinel node biopsy. If any sentinel node is histologically positive by H & E, or histologically suspicious on H & E and confirmed positive by IHC, then the patient must have a completion axillary dissection.
The tumor must be invasive adenocarcinoma on histologic examination with clinical assessment T1-3, N0-1, M0 (see Appendix A for staging information).
Patients must not be participating in any other clinical trials of systemic therapy for early-stage breast cancer. Patients may participate in the following radiationtherapy thearapy:
a. node-positive patients may participate in the National Cancer Institute of Canada Clinical Trials Group protocol MA.20, provided the requirements of
the B-34 protocol continue to be met. (Node-negative B-34 patients may not participate in MA.20.)
b. Node-positive mastectomy patients may participate in Southwest Oncology Group protocol S9927, provided the requirements of the B-34 protocol
continue to be met.
Patients must have an analysis of both estrogen and progesterone receptors on the primary tumor performed prior to randomization. Tumors will be defined as ER or PgR positive if:
1) the Dextran-coated charcoal or sucrose-density gradient method shows them to have = 10 fmol/mg cytosol protein.
2) if using individual laboratory criteria they can be shown to be positive by the enzyme immunoassay
method (EIA) or immunocytochemical assay. “Marginal or borderline,” results (i.e., those not definitively negative) will also be considered positive.
At the time of randomization, the patient must have had the following within the past 3 months:
a. history and physical exam, a bone scan, thoracic and lumbar spine x-rays, and a chest x-ray. Within the past 12 months.
b. patients must have had a gynecologic exam (for women who have a uterus and who will be taking
tamoxifen) and a bilateral mammogram.
At the time of randomization:
a. The postoperative ANC must be = 1500/mm3 (or < 1500/mm3 of the investigator, this represents an ethnic or racial variation of normal),
b. The postoperative platelet count must be = 100,000.
c. There must be postoperative evidence of adequate hepatic function, i.e., -total bilirubin at or below the upper limit of normal (ULN) for the laboratory; and
-alkaline phosphatase < 2.5 x the ULN; and -the SGOT (AST) < 1.5 x the ULN;
d. There must be postoperative evidence of adequate renal function (serum creatinine within or less than the laboratory’s normal range).
Serum albumin and serum calcium must be within normal limits.
A patient with skeletal pain is eligible for inclusion in the study if roentgenological examination fails to disclose metastatic disease. Suspicious findings must be confirmed as benign by x-ray, MRI, or biopsy.
Patients with prior nonbreast malignancies are eligible if they have been disease-free for = 5 years before randomization and are deemed at low risk for recurrence by their treating physicians. Patients with squamous or basal cell carcinoma of the skin that has been effectively treated, carcinoma in situ of the cervix that has been treated by surgery only, or lobular carcinoma in situ (LCIS) of the ipsilateral or contralateral breast treated by hormone therapy and/or surgery only are eligible, even if these were diagnosed within 5 years before randomization.
Patients must have a Zubrod performance status of 0, 1, or 2 (see Appendix B).
Special conditions for eligibility of lumpectomy patients: Irradiation and surgery 08/23/01 Patients treated by lumpectomy and axillary node dissection (or no axillary dissection if sentinel node biopsy is negative) to be followed by breast radiation therapy must meet all the eligibility criteria in Section 5.1 in addition to the following:
a. 5.2.1 Generally, lumpectomy should be reserved for tumors < 5 cm. However, at the investigator’s discretion, patients treated with lumpectomy for tumors = 5 cm are eligible.
b.The margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS). For patients in whom pathologic examination demonstrates tumor present at the line of resection, additional operativ procedures may be performed to obtain clear margins. This is
permissible even if axillary dissection has been performed. Patients in whom tumor is still present at the resected margins after re-excision(s) must undergo total mastectomy to be eligible.
Significant non-malignant bone disease that is likely to interfere with the interpretation of bone x-rays.
Ulceration, erythema, infiltration of the skin or the underlying chest wall (complete fixation), peau d’orange, or skin edema of any magnitude. (Tethering or dimpling
of the skin or nipple inversion should not be interpreted as skin infiltration. Patients with these conditions are eligible.)
Ipsilateral lymph nodes that on clinical examination are found to be fixed to one another or to other structures (cN2 disease).
Suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless there is biopsy evidence that these are not involved
Prior therapy for breast cancer, including irradiation, chemotherapy, biotherapy, and/or hormonal therapy, with the exception of tamoxifen. Tamoxifen may be
given as adjuvant therapy before study entry, but only if it was started within 28 days before randomization. Patients who started tamoxifen within 28 days before
randomization and who are being considered for chemotherapy must have their tamoxifen stopped at the start of chemotherapy.
Prior history of breast cancer, except LCIS.
Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible only if this therapy is discontinued prior to randomization.) Exceptions: patients may use low-dose estrogen vaginal creams or Estring® (see Section 13.1 for dose administration details) for symptomatic vaginal dryness, raloxifene (or other SERMs) for the prevention of osteoporosis, and LHRH agonists/antagonists for the purpose of medical ovarian
ablation as a component of adjuvant therapy for the breast cancer.
Patients currently taking alendronate (Fosamax®) or other bisphosphonates or calcitonin to treat or prevent osteoporosis are not eligible.
Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude a patient from being subjected to any of the treatment options or would prevent prolonged follow-up.
Psychiatric or addictive disorders that would preclude obtaining informed consent.
Pregnancy or lactation at the time of proposed randomization. This protocol excludes pregnant or lactating women because the effects on women have not been studied fully.
Bilateral malignancy or a mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy proof that the mass is not malignant.
Patients with diffuse tumors (as demonstrated on mammography) be considered surgically amenable to lumpectomy.
Patients treated with lumpectomy in whom there is another clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast remnant. Such a mass must be biopsied and demonstrated to be histologically benign prior to randomization or, if malignant, must be surgically removed with clear margins.
Patients in whom the margins of the resected specimen are involved with invasive tumor or ductal carcinoma in situ (DCIS). Additional surgical resections to obtain free margins are allowed. Patients in whom tumor is still present after the additional resection(s) must undergo mastectomy to be eligible.