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A Phase I Study of Cisplatin, Paclitaxel, and RAD001 Patients With Metastatic Breast Cancer

Phase 1
18 Years
Not Enrolling
Breast Cancer

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Trial Information

A Phase I Study of Cisplatin, Paclitaxel, and RAD001 Patients With Metastatic Breast Cancer



- To establish the safety profile and the maximum tolerated dose of the combination of
cisplatin, paclitaxel, and everolimus in patients with metastatic breast cancer.


- To explore the antitumor activity of this regimen, in terms of response rate and time
to progression in these patients.

OUTLINE: This is a multicenter study.

Patients receive cisplatin intravenously (IV) over 1 hour and paclitaxel IV over 1 hour on
days 1, 8, and 15. Patients receive oral everolimus on days 1, 8, 15, and 21. Courses repeat
every 4 weeks in the absence of disease progression and unaccepted toxicity.

After completion of study therapy, patients are followed at 4 weeks.

Inclusion Criteria:


- Histologically confirmed invasive mammary carcinoma

- Stage IV disease

- No locally recurrent breast cancer

- Patients with HER2/neu overexpressing tumors must have received prior trastuzumab
(Herceptin®) in first-line treatment of metastatic breast cancer

- Patients with estrogen receptor- or progesterone receptor-expressing tumors must have
received prior endocrine therapy (i.e., aromatase inhibitors, fulvestrant, tamoxifen,
or ovarian ablation) in first-line treatment of metastatic breast cancer

- No symptomatic brain metastases

- Patients with a history of brain metastases must be clinically stable and not
taking steroids or therapeutic anticonvulsants that are CYP3A4 modifiers

- Patients with asymptomatic brain metastases on prophylactic convulsants that are
CYP3A4 modifiers are not eligible

- Hormone receptor status not specified


- Menopausal status not specified

- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- ANC ≥ 1000/mm^3

- Platelet count ≥ 100,000/mm^3

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN (3 times ULN if liver metastasis present)

- SGOT and SGPT ≤ 1.5 times ULN (3 times ULN if liver metastasis present)

- Alkaline phosphatase ≤ 3 times ULN if liver metastasis present

- Able to swallow and retain oral medication

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- Must be disease-free from prior invasive cancers for > 5 years with the exception of
completely resected basal cell or squamous cell carcinoma of the skin or successfully
treated cervical carcinoma in situ

- No malabsorption syndrome, disease significantly affecting gastrointestinal function,
or ulcerative colitis

- No uncontrolled intercurrent illness including, but not limited to:

- Ongoing or active infection requiring parenteral antibiotics

- Impairment of lung function (i.e., chronic obstructive pulmonary disease or lung
conditions requiring oxygen therapy)

- Symptomatic New York Heart Association class III-IV congestive heart failure

- Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within
the past 6 months

- Uncontrolled hypertension (systolic blood pressure [BP] > 180 mm Hg or diastolic
BP > 100 mm Hg)

- Clinically significant cardiac arrhythmia (i.e., multifocal premature
ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia that
is symptomatic or requires treatment)

- Uncontrolled diabetes

- Psychiatric illness/social situations that would preclude compliance with study

- No known history of uncontrolled or symptomatic neuropathy ≥ grade 2

- No hypersensitivity to paclitaxel, or drugs using the vehicle Cremophor, Chinese
hamster ovary cell products, or other recombinant human antibodies

Exclusion Criteria:


- See Disease Characteristics

- Recovered from all prior treatment

- Must not have exceeded a total cumulative dose of life-time exposure of doxorubicin
hydrochloride ≤ 360 mg/m² or epirubicin hydrochloride ≤ 640 mg/m²

- At least 2 weeks since other prior investigational drugs

- No prior resection of the stomach or small bowel

- No more than 4 prior chemotherapy regimens in the metastatic setting

- This restriction does not include endocrine therapies or single agent biologic
therapies (i.e., trastuzumab)

- Concurrent radiotherapy to painful bone metastases or areas of impending bone
fracture allowed as long as radiotherapy is initiated prior to study entry

- No concurrent trastuzumab

- No concurrent endocrine therapy

- No concurrent CYP3A4 modifiers

- No concurrent herbal supplement

- No other concurrent anticancer therapy (chemotherapy, radiotherapy, surgery,
immunotherapy, hormonal therapy, or biological therapy)

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety profile and maximum tolerated dose

Outcome Description:

The Maximum Tolerated Dose (MTD) will be the dose level at which fewer than 2 of 6 (or 33% of) patients experience dose limiting toxicity (DLT).

Outcome Time Frame:

At 4 weeks

Safety Issue:


Principal Investigator

Ingrid Mayer, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2008

Completion Date:

December 2010

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • stage IV breast cancer
  • Breast Neoplasms



Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Sarah Cannon Cancer Center at Centennial Medical Center Nashville, Tennessee  37203
Vanderbilt-Ingram Cancer Center - Cool Springs Nashville, Tennessee  37064
Vanderbilt-Ingram Cancer Center at Franklin Nashville, Tennessee  37064