Phase II: RAD001 Plus Docetaxel in Patients With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01825265
• Other study ID #: 2004-0758 Phase II
• Status: Withdrawn
• Phase: Phase 2
• First received: April 2, 2013
• Last updated: April 4, 2013
• Start date: November 2005
• Est. completion date: April 2012

Study information

• Verified date: April 2013
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary:

• To assess the safety and tolerability and to find the maximum tolerated dose of the combination administration of RAD001 plus docetaxel when given to patients with metastatic breast cancer who are being considered for standard docetaxel treatment (phase I).

• To characterize the pharmacokinetics of RAD001 and docetaxel when co-administered (phase I).

Secondary:

• To assess the clinical efficacy of the combination regimens in this patient population as shown by response (according to the modified RECIST criteria) (phase II).

• To determine the phosphorylation status of the components of the mTOR signaling pathway and the expression of modifiers of apoptosis in the primary breast tumors, in order to determine whether these markers can be used as predictors of sensitivity to the combination of RAD001 and docetaxel

• To determine the effect of the combination of RAD001 and docetaxel on the expression and phosphorylation of mTOR's targets in the accessible tumor tissue, in order to identify potential pharmacodynamics markers of response to this drug combination

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Docetaxel
40 mg/m^2 IV over 1 hour on Day 1.
• RAD001
30 mg orally on Days 1 and 8.
• Dexamethasone
8 mg orally twice daily for 3 days, starting 24 hours prior to the administration of Docetaxel.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Response to combination RAD001 + docetaxel	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.	3 weeks	No

External Links

•   UT MD Anderson Cancer Center Website