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

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2004-000015-25-LV
• Date of registration: 23/08/2004
• Prospective Registration: Yes
• Primary sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc. Clinical Research and Development
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 06/09/2004
• Target sample size: 1236
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000015-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: CCI-779 + Letrozole vs Placebo + Letrozole

Countries of recruitment

Latvia, Lithuania, Slovakia, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Women aged >18 years.
2. Postmenopausal subjects, defined by at least one of the following:
- >= 60 years of age
- < 60 years of age and amenorrheic for >12 months prior to day 1
- < 60 years of age, without a uterus, and luteinizing hormone (LH) and follicle stimulating hormone (FSH) values within postmenopausal range
- < 60 years of age, amenorrheic for < 12 months prior to day 1, and LH and FSH values within postmenopausal range
- Prior bilateral oophorectomy
- Prior radiation castration with amenorrhea for at least 6 months
3. Histologically and/or cytologically confirmed diagnosis of locally advanced (not amenable to curative surgery and/or radiation) or metastatic breast cancer (Stage 3B 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. Karnofsky performance status (KPS) >60 % (corresponds to Eastern Cooperative Oncology Group [ECOG] performance status 0 to 2).
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

Exclusion criteria:
1. Extensive visceral disease including bilateral diffuse lymphangitic involvement of
the lung with more than 50% lung involvement, evidence of symptomatic 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. Prior radiation therapy to the site of measurable disease for subjects with a solitary measurable lesion.
4. History of inflammatory breast cancer (IBC).
5. More than 1 regimen of chemotherapy (including antibody and/or cytotoxic therapy) in the metastatic setting. Subjects may have received prior adjuvant or neoadjuvant chemotherapy.
6. 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.
7. Hormonal treatment (including aromatase inhibitors) in the metastatic setting with
the exception of prior short-term (< 14 days consecutive) use.
8. Adjuvant trastuzumab (Herceptin) or tamoxifen <= 2 weeks prior to day 1 of treatment on study.
9. Aromatase inhibitors as adjuvant therapy <= 12 months prior to day 1 of treatment on study.
10. Disease refractory (i.e., PD within 6 months from initiation of therapy) to previous adjuvant antiestrogen therapy.
11. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

locally advanced or metastatic breast cancer (stage 3B or 4)

Intervention(s)

Product Name: Temsirolimus
Product Code: CCI-779 10mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Pending
CAS Number: 162635-04-3
Current Sponsor code: CCI-779
Other descriptive name: Temsirolimus, WAY-130779
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Femara (Letrozole 2.5mg )
Product Name: Femara registered trademark (Letrozole) of Ciba Laboratories
Pharmaceutical Form: Tablet
INN or Proposed INN: Letrozole
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Primary end point(s): Overall progression free survival is the primary endpoint of the study, and the clinical activity evaluation will be made using the RECIST guidelines. Non-target lesions, including bone disease, will only be assessed for CR, incomplete response/SD, and PD.

Main Objective: Assessment of overall progression free survival (PFS)

Secondary Objective: Assessment of PFS at 12 and 24 months; Time to treatment failure; Time to progression; Overall response rate; Clinical benefit (CR+PR+ SD > 8 wks/24 wks); Duration of response; Time to initiation of subsequent anticancer therapy; Survival; Safety; Health outcomes; Prognostic markers and pharmacogenomics analysis

Secondary ID(s)

2004-000015-25-SK

3066A1-303-WW