Exemestane With or Without ATN-224 in Treating Postmenopausal Women With Recurrent or Advanced Breast Cancer

• Status: Terminated
• Trial end date: 2009-03-01
• Target enrollment: 0
• Participant gender: Female

Summary

RATIONALE: Exemestane may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. ATN-224 may stop the growth of breast cancer by blocking blood flow to the tumor. It is not yet known whether giving exemestane together with ATN-224 is more effective than giving exemestane alone in treating patients with recurrent or advanced breast cancer.

PURPOSE: This randomized phase II trial is studying the side effects of exemestane given together with or without ATN-224 and to see how well it works in treating postmenopausal women with recurrent or advanced breast cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cancer Research UK
• Treatments: Estrogens; Exemestane; Progesterone; Tetrathiomolybdate

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Recurrent disease after 2-3 years of adjuvant treatment with an anti-estrogen (documented by imaging techniques)

• Advanced disease that has recurred during or after anti-estrogen therapy

• Measurable or evaluable disease by conventional techniques, with ≥ 1 lesion that can be followed for response

• Bone metastases only are eligible provided they have ≥ 1 lytic lesion (not previously irradiated or planned for irradiation) that can be followed by X-ray or CT scanning

• Cutaneous skin metastases only are eligible provided the skin lesions are > 10 mm and can be followed by good quality photography with a ruler included in the photograph

• No clinically apparent brain metastases

• Hormone receptor status must meet 1 of the following criteria:

• Estrogen receptor-positivity

• Score ≥ 3 on a scale (range of 0 to 8), or equivalent score from other grading methods, representing the intensity and percentage of positive-staining tumor cells by immunohistochemistry

• Greater than or equal to 5 fmol/mg protein by ligand binding assay or ELISA

• Progesterone receptor-positivity

• Score ≥ 3 on a scale (range of 0 to 8) or equivalent score from other grading methods, representing the intensity and percentage of positive-staining tumor cells by immunohistochemistry

• No HER-2 overexpression, defined as gene amplification by fluorescence in situ hybridization [FISH] OR 3+ overexpression by IHC)

PATIENT CHARACTERISTICS:

• Postmenopausal as defined by any of the following:

• Surgical or radiation-induced

• No menstrual periods for 12 consecutive months with no other biological or physiological cause in women with an intact uterus

• Age ≥ 55 years

• WHO performance status 0-2

• Life expectancy ≥ 6 months

• Hemoglobin ≥ 9.0 g/dL

• ANC ≥ 1.5 x 10^9/L

• Platelet count ≥100 x 10^9/L

• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT and/or AST ≤ 2.5 times ULN (5 times ULN if due to tumor)

• Creatinine clearance ≥ 50 mL/min

• No history of malabsorption syndromes or other gastrointestinal disorders that may affect SOD1 inhibitor ATN-224 absorption, including any of the following:

• Bowel obstruction

• Celiac disease

• Sprue

• Cystic fibrosis

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to SOD1 inhibitor ATN-224, omeprazole (or other proton pump inhibitor), or exemestane

• No non-malignant systemic disease including active uncontrolled infection

• No serologic positivity for hepatitis B, hepatitis C, or HIV

• No concurrent congestive heart failure

• No history of NYHA class III-IV cardiac disease

• No other concurrent malignancy, except adequately treated cone-biopsied carcinoma in situ of the uterine cervix, basal cell or squamous cell carcinoma of the skin

• Cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 5 years, and are deemed at low risk for recurrence are eligible

• No other condition which, in the investigator's opinion, would not make the patient a good candidate for this study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior therapy (alopecia allowed)

• At least 1 year since prior bilateral oophorectomy

• Prior adjuvant or neoadjuvant treatment with tamoxifen allowed

• Prior adjuvant therapy with a non-steroidal aromatase inhibitor allowed

• More than 4 weeks since prior immunotherapy or chemotherapy (6 weeks for nitrosoureas and mitomycin-C)

• More than 4 weeks since prior major thoracic and/or abdominal surgery

• More than 3 weeks since prior endocrine therapy

• More than 4 weeks since prior and no concurrent radiotherapy (except to control pain or prevent fracture)

• No prior exemestane

• Concurrent iron-containing vitamins or supplements are allowed

• No concurrent luteinizing hormone-releasing hormone analog

• No concurrent oral bisphosphonates (IV bisphosphonates allowed)

• No concurrent chronic steroid therapy for concurrent illness or cancer (short-term steroid use for concurrent illness allowed [e.g., for acute asthma])

• No concurrent copper- or zinc-containing vitamins or supplements

• No concurrent participation in another interventional clinical study (participation in an observational study allowed)

• No other concurrent copper-binding drug (e.g., penicillamine or trientine)

• No other concurrent anticancer therapy or investigational agent