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

NCT00674557 | Terminated Phase 2

• 4 other identifiers: CRUK-CR0207-22CDR0000595074EUDRACT-2007-005752-16EU-20850
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; HER2-negative breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-positive breast cancer

Outcome Measures

Primary Outcomes (2)

• Progression-free survival

• Safety

Secondary Outcomes (10)

• Response rate (complete and partial response) overall and at 16 and 24 weeks

• Rate of stable disease for ≥ 16 and ≥ 24 weeks

• Response duration

• Clinical benefit rate (complete and partial response, stable disease) at 16 and 24 weeks

• Time (in days) taken after starting SOD1 inhibitor ATN-224 to achieve target serum ceruloplasmin level (5 to 15 mg/dl)

Interventions

SOD1 inhibitor ATN-224 DRUG

exemestane DRUG

protein expression analysis GENETIC

proteomic profiling GENETIC

laboratory biomarker analysis OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (1)

Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford

Oxford, England, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tetrathiomolybdate; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Adrian L. Harris, MD

  Churchill Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 7, 2008
• First Posted: May 8, 2008
• Study Start: June 1, 2008
• Study Completion: March 1, 2009
• Last Updated: July 10, 2013

Record last verified: 2009-03

Locations

GB (1)