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 - HORIZON trial
- Conditions
- locally advanced or metastatic breast cancer (stage 3B, 3C, or 4)
- Registration Number
- EUCTR2004-000015-25-GB
- Lead Sponsor
- Wyeth Research Division of Wyeth Pharmaceuticals Inc. Clinical Research and Development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 1236
1. Women aged >=18 years.
2. Postmenopausal subjects, defined by at least one of the following:
>= 60 years of age
Physiological Menopause: < 60 years of age and amenorrheic for >=12 months prior to day 1
< 60 years of age, amenorrheic for < 12 months prior to day 1, and LH and FSH values within postmenopausal range. LH/FSH values must not be influenced by effects of medication (not chemically dependent, i.e., LHRH agonist)
Surgical Menopause: Prior bilateral oophorectomy
Prior radiation castration with amenorrhea for at least 6 months
3. Histologically and/or cytologically confirmed initial diagnosis of locally advanced (not amenable to curative surgery and/or radiation) or metastatic breast cancer (Stage 3B, 3C, or 4 respectively, by American Joint Committee on Cancer Criteria).
4. Documented estrogen receptor positive (ER+) and/or progesterone positive (PR+) tumors based on most recently analyzed biopsy.
5. At least 1 measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST).
6. Screening laboratory values within the following parameters:
ANC >=1.5x109/L (1500/mm3)
Platelet count >=100x109/L (100,000/mm3)[ >=80x109/L (80,000/mm3)] for subjects residing in mainland China
Hemoglobin >=8.0 g/dL (80g/L)
Serum creatinine =<1.5x upper limit of normal (ULN)
Total bilirubin =<1.5xULN
AST and ALT =<3xULN [=<5x ULN if liver metastases are present]
Fasting serum cholesterol =<350 mg/dL (9.0 mmol/L)
Fasting serum triglycerides =<400 mg/dL (4.56 mmol/L)
Serum calcium=<12.5 mg/dL (3.1 mmol/L) [value may have been obtained following initiation of treatment with bisphosphonates]
7. Karnofsky performance status (KPS) >=60 % (corresponds to Eastern Cooperative Oncology Group [ECOG] performance status 0 to 2).
8. Life expectancy of at least 6 months.
9. Ability to swallow whole tablets.
10. Signed and dated institutional review board (IRB) or independent ethics committee (IEC) approved informed consent form before any protocol-specific screening procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Extensive visceral disease including bilateral diffuse lymphangitic involvement of the lung with more than 50% lung involvement, known or suspected central nervous system (CNS) metastases, extensive hepatic involvement defined as involvement of more than one third of the liver confirmed by sonogram and/or CT scan.
2. Subjects with bone as the only site of disease.
3. History of inflammatory breast cancer (IBC).
4. Any other cancer within 5 years prior to screening with the exception of contralateral breast carcinoma, appropriately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
5. Presence of unstable angina, recent myocardial infarction (within 6 months prior to screening), use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, or known pulmonary hypertension.
6. More than 1 regimen of chemotherapy (including antibody, immunotherapy, biological, and/or cytotoxic therapy) in the locally advanced or metastatic setting. (Note: patients must have documented progression following chemotherapy in the locally advanced or metastatic setting. However, in the case of patients who receive not more than 1 cycle of the prescribed chemotherapy regimen in the locally advanced or metastatic setting, documented progression is not required). Subjects may have received prior adjuvant or neoadjuvant chemotherapy.
7. Chemotherapy or immunosuppressive agents =<2 weeks prior to day 1 of treatment on study, with the exception of systemic corticosteroids administered for physiologic replacement, or as an antiemetic after discussion with the medical monitor.
8. Hormonal treatment (including aromatase inhibitors) in the locally advanced or metastatic setting with the exception of prior short-term (< 14 days consecutive) use. Surgical menopause (e.g. oophorectomy) after diagnosis of locally advanced or metastatic disease is considered as a line of hormonal therapy.
9. Adjuvant trastuzumab (Herceptin) or tamoxifen =<2 weeks prior to day 1 of treatment on study.
10. Aromatase inhibitors as adjuvant therapy =<12 months prior to day 1 of treatment on study.
11. Disease refractory (i.e., PD within 6 months from initiation of therapy) to previous adjuvant antiestrogen therapy.
12. Major surgery, biological therapy, immunologic therapy or local radiotherapy (subjects must not have had prior cumulative radiotherapy to more than 25% of the marrow) =<2 weeks prior to day 1 of treatment on study.
13. Immunocompromised subjects, including subjects known to be human immunodeficiency virus (HIV) positive and/or acute or chronic hepatitis B (HbsAg) positive or hepatitis C virus (anti-HCV) positive.
14. Prior treatment with mTOR inhibitors.
15. Known hypersensitivity to letrozole or CCI-779.
16. Any investigational agents =< 4 weeks prior to day 1 of treatment on study
17. Any other illness that, in the investigator’s judgment, will substantially increase the risk associated with the patient’s participation in the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method