Phase I Oral mTOR Inhibitor RAD001 in Combo w/ Capecitabine for Metastatic Breast

NCT00473005 | Terminated Phase 1 DMC

• 2 other identifiers: BRSMTS001097494
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

In order to improve the survival of metastatic breast patients, it is important to investigate the use of novel therapeutic agents combined with known active agents in the treatment of breast cancer. This is a phase I study evaluating the maximum tolerated doses and toxicities of RAD001 in combination with capecitabine for the treatment of metastatic breast cancer. RAD001 (INN: everolimus) is a novel macrolide, which is being developed as an antiproliferative drug with applications as an immunosuppressant and anticancer agent. Phase I trials in patients with solid tumors have shown that treatment with RAD001 is well-tolerated with a minimal side effect profile. Capecitabine (Xeloda, Roche) is an oral fluoropyrimidine that was approved in 1998 for the treatment of patients with metastatic breast cancer. The all-oral regimen of RAD001 with capecitabine is an attractive approach as the treatment of metastatic breast cancer has not yet proven to be curative. We also want to find out what possible benefit this combination of drugs might have on treating your cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Using three cohorts of patients with fixed dosing of capecitabine in combination with increasing doses of RAD001, the maximum tolerated doses and toxicities will be determined.

  Measured at baseline and before every other cycle.

Secondary Outcomes (1)

• Tumor response

  After every two cyclescycles (six weeks) of therapy for the first four cycles, then after every three cycles (nine weeks) for the remainder of the first year, then every four cycles (12 weeks).

Interventions

Capecitabine DRUG

825 mg/m2 bid, Oral

Also known as: Xeloda, Roche

RAD001 DRUG

2.5mg QOD, 2.5mg QD, 5.0mg QD, Oral

Also known as: Everolimus, Zortress, Certican, Afinitor

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed metastatic breast cancer.
• Measurable disease either by clinical exam or radiographs.
• Patients must be fully recovered from acute toxicity of prior therapy.
• Patients must not have received prior therapy with capecitabine.
• Patients must not have received more than 3 prior chemotherapy regimens for metastatic breast cancer.
• Patients must not be receiving concurrent endocrine therapy or immunotherapy.
• Patients must have an expected survival of at least 3 months.
• Patients should have ECOG performance status 0 or 1 (KPS 100-80%).
• Patients should have adequate bone marrow, hepatic and renal function.
• WBC \>= 3000/mm\^3,
• ANC \> 1500,
• Hgb \> 9 g/dL,
• Platelets \>= 100,000/mm\^3,
• total bilirubin\<1 .5 mg/dL,
• AST/ALT\<2.5 x normal {\<= 5x ULN in patients with liver metastases}

You may not qualify if:

• Patients who have received other chemotherapy or endocrine therapy and not recovered from acute toxicity of previous therapy.
• Patients who have received radiotherapy within 4 weeks prior to start of this trial.
• Patients who have undergone major surgery within 2 weeks of study enrollment.
• Patients with known evidence of brain metastases or leptomeningeal disease, , including patients who continue to require glucocorticoids for brain or leptomeningeal metastases..
• Patients with a history of other cancers except curatively-treated carcinoma of the cervix in situ or non-melanomatous skin cancer. Patients with other cancers thought to be cured may be entered into the trial after discussion with and approval of the study chair.
• Patients with an active serious infection or other serious underlying medical condition that would impair their ability to receive protocol treatment.
• Patients with bone metastases as their only site of measurable disease.
• Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent.
• Pregnant or breast-feeding patients.
• Patients not using adequate methods of birth control if still of child-bearing potential.
• Patients who have received prior therapy with capecitabine.
• Patients who have received more than 3 prior chemotherapy regimens for metastatic breast cancer.
• Patients receiving other investigational therapy.
• Patients who have received prior treatment with experimental therapy within 30 days prior to start of trial.
• Patients who receive chronic systemic steroids or other immunosuppressive agents.

Sponsors & Collaborators

• Stanford University: lead
• Novartis: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Dr. Ellie Guardino MD/PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 11, 2007
• First Posted: May 14, 2007
• Study Start: August 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 28, 2012

Record last verified: 2012-05

Locations

US (1)