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Phase II Trial of CCI-779 (Temsirolimus) in Patients With Locally Advanced or Metastatic Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Male Breast Cancer, Recurrent Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

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Trial Information

Phase II Trial of CCI-779 (Temsirolimus) in Patients With Locally Advanced or Metastatic Breast Cancer


I. Determine the overall activity (complete response, partial response, and stable disease)
of temsirolimus in patients with recurrent locally advanced or metastatic breast cancer.

II. Compare the activity of temsirolimus in patients whose primary tumors have mutations in
the PIK3CA or PTEN gene with those whose tumors do not have a mutation in the PIK3CA
gene.Correlate the antitumor activity of temsirolimus with alterations in expression of
genes in the PI3K pathway in primary tumor biopsy specimens.

OUTLINE: This is a multicenter study.

Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats
every 28 days in the absence of disease progression or unacceptable toxicity.

Tissue collected from the primary tumor is examined by gene sequencing and
immunohistochemistry for gene mutations and protein expression in the PI3K pathway,
including PIK3CA and PTEN mutations. Fluorescent in situ hybridization (FISH) is used to
detect alterations in PIK3CA gene copy number. Immunohistochemical staining is used for
cyclin D1, PTEN, pAKT, SGK-1, p-mTOR, pE-BP1, and phospho and total S6 kinase.

Inclusion Criteria:

- Histologically or cytologically confirmed breast cancer

- Recurrent locally advanced disease not amenable to local therapy (i.e., surgery
and radiotherapy)

- Metastatic disease

- Either the primary or metastatic tumor must meet ≥ 1 of the following criteria:

- Estrogen receptor positive (≥ 1% by immunohistochemical staining)

- Progesterone receptor positive (≥ 1% by immunohistochemical staining)

- HER2/neu overexpression (3+ by immunohistochemical staining or positive by
fluorescent in situ hybridization [FISH])

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- Tissue samples available for correlative studies

- Brain metastases allowed provided all of the following criteria are met:

- Controlled by prior surgery or radiotherapy

- Neurologically stable and off steroids for ≥ 4 weeks

- ECOG performance status 0-1

- Male or female

- Menopausal status not specified

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin normal

- AST/ALT ≤ 3 times upper limit of normal (ULN)

- Creatinine ≤ 2.0 times ULN

- Cholesterol ≤ 350 mg/dL (fasting)

- Triglycerides ≤ 400 mg/dL (fasting)

- Albumin ≥ 3.3 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier-method contraception

- No uncontrolled illness, including, but not limited to, any of the following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Uncontrolled symptomatic cardiac arrhythmia

- Psychiatric illness or social situation that would preclude compliance with
study requirements

- No known hypersensitivity to macrolide antibiotics (e.g., erythromycin,
clarithromycin, or azithromycin)

- See Disease Characteristics

- Recovered from prior therapy

- No prior rapamycin or any other mTOR inhibitor

- At least 1 week since prior hormonal agents, except for premenopausal women receiving
a gonadotropin-releasing hormone (GnRH) agonist with subsequent progression*

- At least 3 weeks since prior chemotherapy

- At least 3 weeks since prior monoclonal antibody therapy

- No concurrent radiotherapy

- No concurrent herbal preparations

- No concurrent corticosteroids except low-dose corticosteroids as replacement for
adrenal insufficiency or for short-term (< 5 days) use

- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or

- No other concurrent CYP3A4 inducers (e.g., rifampin or Hypericum perforatum [St.
John's wort])

- No concurrent prophylactic hematopoietic colony-stimulating factors

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies

- No other concurrent investigational agents

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall activity (complete response, partial response, and stable disease) of temsirolimus

Outcome Time Frame:

Up to 24 months

Safety Issue:


Principal Investigator

Gini Fleming

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2006

Completion Date:

Related Keywords:

  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male



Washington University School of Medicine Saint Louis, Missouri  63110
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470