RAD001 Plus Docetaxel in Patients With Metastatic Breast Cancer

NCT00253318 | Terminated Phase 1

• 2 other identifiers: 2004-0758NCI-2010-00840
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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 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

Conditions

Breast Cancer

Keywords

Neoplasm Metastasis; Breast Cancer; Docetaxel; RAD001; Taxotere

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of combination of RAD001 plus Docetaxel

  3 week cycles

Study Arms (1)

RAD001 + Docetaxel

EXPERIMENTAL

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

Drug: Docetaxel; Drug: RAD001; Drug: Dexamethasone

Interventions

Docetaxel DRUG

40 mg/m\^2 IV over 1 hour on Day 1.

Also known as: Taxotere

RAD001 + Docetaxel

RAD001 DRUG

30 mg orally on Days 1 and 8.

RAD001 + Docetaxel

Dexamethasone DRUG

8 mg orally twice daily for 3 days, starting 24 hours prior to the administration of Docetaxel.

Also known as: Decadron

RAD001 + Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• 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 Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
• 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.
• 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.
• 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.
• Normal renal function as shown by serum creatinine \< or = 1.5 times Upper Limit of Normal (ULN).
• 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
• Performance Status 0-2 on the World Health Organization (WHO) scale.

You may not qualify if:

• 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.
• Patients with a history of thromboembolism within the prior 6 months or active thrombophlebitis.
• 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.
• 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.
• Patients with an uncontrolled infection.
• Patients with a known history of HIV seropositivity.
• 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).
• 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).
• 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).
• Patients who received any other investigational drugs within the preceding 30 days.
• Patients who have received mitomycin C or nitrosourea.
• 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.
• 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.
• 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.
• Patients with a history of noncompliance to medical regimens.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77230-1439, United States

Location

Related Links

• UT MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Docetaxel; Everolimus; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Sirolimus; Macrolides; Lactones; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Stacy Moulder, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2005
• First Posted: November 15, 2005
• Study Start: November 1, 2005
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: April 27, 2025

Record last verified: 2023-10

Locations

US (1)