A phase 3 randomized, placebo-controlled, double-blind study of oral CCI-779 administered in combination with letrozole vs. letrozole alone as first line hormonal therapy in postmenopausal women with locally advanced or metastatic breast cancer

Not Applicable

Conditions: -C50 Malignant neoplasm of breast
Malignant neoplasm of breast
C50

Registration Number: PER-075-04

Lead Sponsor: WYETH RESEARCH,

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

• Women 18 years of age or older.
• Postmenopausal women,
• Have an initial diagnosis of locally advanced or metastatic breast cancer (not treatable by surgery and / or radiation, Stage 3B, 30, or 4, respectively, according to the American Joint Committee on Cancer Criteria) confirmed histologically and / or cytologically.
• Positive estrogen receptor (ER +) and / or progesterone positive (PR +) tumors, documented on the basis of the most recently analyzed biopsy.
• At least 1 lesion that can be measured (measurable), defined according to the criteria of Response Evaluation Criteria in Solid Tumors (RECIST).
• Serum creatinine <1.5 x. upper limit
• Functional status evaluation of Kamofsky (KPS)> 60% (corresponding to the functional status of the Eastem Cooperative Oncology Group [ECOG] between 0 and 2).
• Life expectancy of at least 6 months.
• Ability to swallow whole tablets.
• Have an informed consent form approved by the Institutional Review Committee (IRB) or by the Independent Ethics Committee (IEC) signed and dated before carrying out any specific protocol selection procedure.

Exclusion Criteria

• Extended visceral disease, including involvement of diffuse bilateral lymphangitis of the lungs, with more than 50% of the lung involved; metastasis in the central nervous system (CNS) known or suspected; extensive liver involvement, defined as the involvement of more than one third of the liver, confirmed by ultrasound and / or computed tomography (CT).
• Subjects with bone as the only sector affected by the disease.
• History of inflammatory breast cancer (IBC).
• Any other cancer within 5 years prior to selection, with the exception of contralateral mammary carcinoma, duly treated cervical cancer in situ, or basal or squamous cell carcinoma of the skin duly treated.
• Presence of unstable angina, recent myocardial infarction (within 6 months prior to detection), use of permanent maintenance therapy for life-threatening ventricular arrhythmia or proven pulmonary hypertension.
• More than 1 chemotherapy regimen (including antibody therapy, immunotherapy, biological therapy, and / or cytotoxic) in locally advanced or metastatic cases. (Note: patients should have documented progression after chemotherapy in locally advanced or metastatic cases, however, in case of patients who have received no more than 1 cycle of the chemotherapy regimen indicated in locally advanced or metastatic cases, it is not necessary have documented progression). Subjects may have received neoadjuvant or adjuvant chemotherapy previously.
• Chemotherapy or immunosuppressive agents less than 2 weeks before day 1 of treatment within the study, except for the use of systemic corticosteroids given as a physiological replacement or as an antiemetic, after analyzing the issue with the medical monitor.
• Hormone treatment (including aromatase inhibitors) for metastatic or locally advanced control, except for short-term previous use (less than 14 consecutive days). Surgical menopause (eg, oophorectomy) after diagnosis of locally advanced or metastatic disease is considered a line of hormone therapy.
• Trastuzumab (Herceptin®) or tamoxifen as adjuvant <2 weeks before day 1 of study treatment.
• Aromatase inhibitors as adjuvant <12 months before day 1 of the study treatment.
• Refractory disease (that is, progressive disease within 6 months of therapy initiation) before previous adjuvant therapy with antiestrogens.
• Major surgery, biological therapy, immunotherapy, or local radiotherapy (subjects must not have had previous cumulative radiation therapy in more than 25% of the bone marrow) ^ weeks before day 1 of the study treatment.
• Subjects with immunological commitment, includes those subjects known to be positive for human immunodeficiency virus (HIV) or acute or chronic hepatitis B virus (HBsAg) or positive for Hepatitis C virus (anti-HCV) .
• Previous treatments with mTOR inhibitors.
• Known hypersensitivity to letrozole or CCI-779.
• Any research agent <4 weeks before day 1 of the study treatment.
• Any other disease that, in the opinion of the investigator, substantially increases the risk associated with the patient´s participation in the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br>Outcome name:The evaluation of the clinical activity will be carried out using the guidelines established in the Criteria for Evaluation of Responses in Solid Tumors (RECIST)<br>Measure:General survival without progression of the disease<br>Timepoints:At the end of treatment<br>

Secondary Outcome Measures

Name	Time	Method
<br>Outcome name:Measurement of PFS<br>Measure:Change in PFS at 12 months and at 24 months.<br>Timepoints:12 and 24 months<br>;<br>Outcome name:Time to treatment failure and time to disease progression<br>Measure:Time to treatment failure and time to disease progression<br>Timepoints:During treatment<br>;<br>Outcome name:General response index, Clinical benefit (CR + PR + SD> 8 weeks / 24 weeks), duration of response<br>Measure:General response index, Clinical benefit (CR + PR + SD> 8 weeks / 24 weeks), duration of response<br>Timepoints:8 weeks / 24 weeks<br>

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