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Phase II, Open Label, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of the Combination RAD001 Plus Docetaxel in Patients With Metastatic Breast Cancer


Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer

Thank you

Trial Information

Phase II, Open Label, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of the Combination RAD001 Plus Docetaxel in Patients With Metastatic Breast Cancer


Docetaxel is a drug approved for the treatment of metastatic breast cancer in patients who
are either newly diagnosed or have failed earlier chemotherapy. RAD001 is an investigational
drug that has shown to have anticancer properties. It also works by weakening the immune
system. RAD001 works by blocking some of the steps required for cancer growth. The
researcher hopes that RAD001 may increase the anticancer activity of docetaxel.

If you are found to be eligible to take part in this study, you will receive docetaxel by
vein on Day 1 over one hour. RAD001 will be given by mouth on Days 1 and 8. RAD 001 will be
given on an empty stomach or after a light meal. You will repeat this treatment every 21
days. Three (3 ) weeks equals 1 cycle.

Patients who participated on the first phase of study numbered 2004-0758 will be eligible
for the study. The study will done using the highest dose of RAD001 and docetaxel that was
found to be safe and effective during the first phase of the study.

Dexamethasone will be given by mouth twice a day for 3 days, starting the day before you
receive docetaxel. Dexamethasone helps decrease the risk of and control nausea, vomiting,
and fluid retention.

Blood (between 1-2 teaspoons) will be drawn for routine tests at each visit. X-rays and
scans (CT or MRI) will be done every 6 weeks to see if the tumor is responding to treatment.

After 6 cycles of the combination, docetaxel will be stopped and you will continue to take
RAD001 alone. However, you may be able to take more than 6 cycles of the combination if you
are not having any side effects and is found to be of benefit by your primary doctor.

Once you go off treatment, you will have a physical exam, including routine blood tests (1-2
teaspoons).

This is an investigational study. Docetaxel is approved by the FDA and commercially
available for the treatment of breast cancer. RAD001 is authorized for use in research only.
About 65 patients will take part in the study. All will be enrolled at M. D. Anderson.


Inclusion Criteria:



1. 18 years of age or older.

2. Diagnosis of metastatic breast cancer with at least one measurable or evaluable
lesion. For the phase II portion of the study patients will be required to have
measurable disease. Response will be determined using the RECIST criteria.

3. No limit on the prior number of chemotherapies for the phase I portion of the study.
No more than one prior chemotherapy regimen for the phase II portion of the study.

4. Signed informed consent to participate in the study must be obtained from patients
after they have been fully informed on the nature and potential risks by the
investigator with the aid of written information.

5. Adequate bone marrow function as shown by: Absolute neutrophil count (ANC) > or = 1.5
times 10(9)/L, Platelets > or = 100 times 10(9)/L, Hgb > or = 10g/dL.

6. Normal renal function as shown by serum creatinine < or = 1.5 times Upper Limit of
Normal (ULN).

7. Hepatic Function Variables:

- Bilirubin < or = ULN

- Alkaline phosphatase < or = 5 times ULN. If alkaline phosphatase is < or = 2.5
times ULN, ALT/AST must be < or = 2.0 times ULN. If alkaline phosphatase is >
2.5 but < or = 5 times ULN, ALT/AST must be < or = 1.5 times ULN

8. Performance Status 0-2 on the World Health Organization (WHO) scale.

Exclusion Criteria:

1. Patients enrolled in the Phase I portion of the trial may have received prior
docetaxel in the adjuvant or metastatic setting. Patients enrolled in the Phase II
portion of the trial will not be considered eligible if they have received prior
docetaxel as treatment for metastatic breast cancer. For the purposes of this
protocol, patients who develop systemic metastasis < 6 months from adjuvant docetaxel
will be considered to have had treatment with docetaxel for metastatic breast cancer
and will be ineligible for protocol participation.

2. Patients with a history of thromboembolism within the prior 6 months or active
thrombophlebitis.

3. For the phase I portion of the study, patients with grade > 2 neuropathy, for the
phase II portion of the trial, patients with > or = grade 2 neuropathy.

4. For the phase I portion of the trial, patients with treated brain metastasis that are
stable for 3 months will be eligible for protocol participation. However, patients
with brain metastasis will be excluded from the phase II portion of the trial.

5. Patients with an uncontrolled infection.

6. Patients with a known history of HIV seropositivity.

7. Patients with an active, bleeding diathesis, or on oral anti-vitamin K medication
(except patients receiving 1 mg of warfarin to prevent central venous catheter
thrombosis).

8. Patients with other concurrent severe and/or uncontrolled medical disease which could
compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled
hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic
heart disease, myocardial infarction within six months, chronic liver or renal
disease, active upper GI tract ulceration).

9. Patients with impairment of gastrointestinal function or gastrointestinal disease
that may significantly alter the absorption of RAD001 (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel
resection).

10. Patients who received any other investigational drugs within the preceding 30 days.

11. Patients who have received mitomycin C or nitrosourea.

12. Patients receiving anti-neoplastic therapy less than 14 days prior to entry onto this
study or who have not recovered from the toxic effects of such therapy.

13. Patients who received radiation therapy within 3 weeks prior to entry on this study
or who have not recovered from the toxic effects of such therapy.

14. Patients who had surgery within 2 weeks prior to entry on this study or who have not
recovered from the side effects of such therapy.

15. Patients with a history of noncompliance to medical regimens.

16. Patients unwilling to or unable to comply with the protocol.

17. Patients being treated with drugs recognized as being strong inhibitors or inducers
of the isoenzyme CYP3A4 or patients taking lithium chloride.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Number of Participants with Response to combination RAD001 + docetaxel

Outcome Description:

Clinical efficacy of the combination regimens in the participant population as shown by response (according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria). Response evaluated with each 3 week cycle.

Outcome Time Frame:

3 weeks

Safety Issue:

No

Principal Investigator

Stacy Moulder, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2004-0758 Phase II

NCT ID:

NCT01825265

Start Date:

November 2005

Completion Date:

April 2012

Related Keywords:

  • Breast Cancer
  • Neoplasm Metastasis
  • Breast Cancer
  • Docetaxel
  • RAD001
  • Taxotere
  • Breast Neoplasms

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