Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Letrozole With or Without CCI-779 in Treating Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

Basic Trial Information

Objectives

1. Compare the objective response rate of postmenopausal women with locally advanced or metastatic breast cancer treated with letrozole with vs without CCI-779.
2. Compare the overall response rate, including stable disease lasting at least 6 months, time to progression, and time to treatment failure, in patients treated with these regimens.
3. Compare the pharmacokinetics of these regimens in these patients.
4. Compare the safety of these regimens in these patients.
5. Correlate the pharmacodynamics of these regimens with clinical response in these patients.
6. Compare the impact of these regimens on patient-reported health outcomes.
7. Compare progression-free rates at various intervals in patients treated with these regimens.
8. Compare duration of response and overall survival of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed breast cancer
  • Locally advanced disease
    • Not amenable to curative surgery and/or radiotherapy

    OR

  • Metastatic disease
    • Stage IIIB, IIIC, or IV

• Measurable disease

• Presenting with de novo advanced or metastatic cancer OR tumor progression in 1 of the following ways:
  • During or after completing adjuvant tamoxifen therapy
  • During first-line metastatic therapy with tamoxifen

• Disease limited to the bone allowed provided at least 2 bone metastases exist (including at least 1 osteolytic lesion), each having a unilateral dimension of at least 1 cm

• No CNS metastases

• No hepatic metastases that constitute extensive visceral disease or are acutely life threatening

• No symptomatic pulmonary lymphangitic metastases

• No prior inflammatory breast cancer

• Must be appropriate to receive endocrine therapy as treatment for advanced disease

• Hormone receptor status:
  • Estrogen and/or progesterone receptor positive

Prior/Concurrent Therapy:

Biologic therapy

• At least 6 months since prior trastuzumab (Herceptin)
• At least 3 weeks since prior biologic therapy
• At least 3 weeks since prior immunologic therapy
• No concurrent immunotherapy
• No concurrent prophylactic use of growth factors except erythropoietic agents

Chemotherapy

• At least 6 months since prior adjuvant chemotherapy
• No prior chemotherapy for locally advanced disease or in the metastatic setting
• No concurrent cytotoxic chemotherapy
• No prior CCI-779

Endocrine therapy

• See Disease Characteristics
• At least 3 weeks since prior hormonal therapy (adjuvant or metastatic setting)
• Prior adjuvant antiestrogens allowed
• No prior aromatase inhibitors
• No other concurrent aromatase inhibitors
• No concurrent hormonal agents
• Concurrent corticosteroids for physiologic replacement allowed

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior local radiotherapy
• No prior radiotherapy to more than 25% of the marrow
• Concurrent radiotherapy allowed with the following criteria:
  • Palliative radiotherapy allowed for pain control or other reasons with no curative intent
  • Tumor progression should be ruled out before therapy
  • No radiotherapy to more than 25% of the bone marrow
  • No radiotherapy including all of the target lesions

Surgery

• At least 3 weeks since prior surgery

Other

• At least 3 weeks since prior immunosuppressive agents
• No ongoing maintenance therapy for life-threatening ventricular arrhythmia
• No other concurrent anticancer therapy
• No other concurrent investigational therapy
• No concurrent immunosuppressive therapy
• No concurrent ketoconazole
• No concurrent phenobarbitol, carbamazepine, or phenytoin
• No concurrent Hypericum perforatum (St. John's wort)

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Postmenopausal defined by 1 of the following:
  • Radiation-induced menopause or surgical bilateral oophorectomy
  • Intact uterus and any of the following:
    • Older than 55 years of age
    • No menses for the past 5 years
    • 55 years of age or younger and no menses for at least the past 12 months (but has had menses in the past 5 years) and postmenopausal levels of follicle-stimulating hormone (FSH) (i.e., concentration greater than the lower limit of normal)
  • No intact uterus and either of the following:
    • Older than 55 years of age
    • 55 years of age or younger and has FSH levels in the postmenopausal range

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 8.5 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN (5 times ULN if liver metastases are present)
• Hepatitis B surface antigen negative
• Hepatitis C virus negative

Renal

• Creatinine no greater than 1.5 times ULN
• Calcium no greater than 11 mg/dL (2.75 mmol/L)

Cardiovascular

• No myocardial infarction within the past 6 months
• No unstable angina
• No known pulmonary hypertension

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 weeks after study participation
• Cholesterol no greater than 350 mg/dL (9.0 mmol/L)
• Triglycerides no greater than 400 mg/dL (4.56 mmol/L)
• Able to swallow whole tablets
• HIV negative
• Not immunocompromised
• No other malignancy within the past 5 years except appropriately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, or contralateral breast cancer
• No other serious concurrent illness
• No known hypersensitivity to any of the components in letrozole or CCI-779
• No other major illness that would increase the risk associated with study participation

Expected Enrollment

Approximately 108 patients (36 per treatment arm) will be accrued for this study.

Outline

This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive oral letrozole and oral CCI-779 daily.

• Arm II: Patients receive oral letrozole on days 1-14 and oral CCI-779 on days 1-5. Courses repeat every 14 days.

• Arm III: Patients receive oral letrozole daily on days 1-5. Courses repeat every 14 days. Patients with disease progression may cross over to oral CCI-779 alone on days 1-5 every 14 days.

In all arms, treatment continues for up to 24 months in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days and then every 3 months thereafter.

Trial Contact Information

Trial Lead Organizations

Seidman Cancer Center at University Hospitals/Case Medical Center

Beth Overmoyer, MD, FACP, Protocol chair		Ph: 216-844-8573 Email: bao4@po.cwru.edu

Registry Information
Official Title		A Phase II, Randomized, Open-Label Study Of Letrozole In Combination With Two Dose Levels And Schedules Of Oral CCI-779, Or Letrozole Alone, In Postmenopausal Women With Locally Advanced Or Metastatic Breast Cancer
Trial Start Date		2003-03-17
Registered in ClinicalTrials.gov		NCT00061971
Date Submitted to PDQ		2003-04-14
Information Last Verified		2004-07-26
NCI Grant/Contract Number		P30-CA43703

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