December 14, 2006 |
December 2, 2008 |
December 2006 |
To determine the clinical activity of oral daily rapamycin administered in combination with weekly intravenous trastuzumab in patients with HER2
overexpressing advanced breast cancer [ Time Frame: Determine the proportion of patients who are progression-free (CR, PR and stable disease) at 16 weeks ] [ Designated as safety issue: No ] |
Same as current |
Complete list of historical versions of study NCT00411788 on ClinicalTrials.gov Archive Site |
- To determine the objective response rate according to RECIST criteria, duration of response, and time to progression in patients with HER2 overexpressing
advanced breast cancer receiving trastuzumab and rapamycin [ Time Frame: upon completion of study ] [ Designated as safety issue: No ]
- To determine the rate of cardiac dysfunction in patients treated with the combination of trastuzumab and rapamycin [ Time Frame: Upon completion of study ] [ Designated as safety issue: Yes ]
- To determine pre and post therapy changes in the levels, phosphorylation status and/or subcellular localization of the affected signal transduction
molecules HER2, Akt, S6K and 4EBP1 in blood and tumor tissues [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]
- To determine if currently available RNA expression profiles associated with response to Herceptin will be predictably altered in tumors treated with
trastuzumab and rapamycin, and will further elucidate the mechanism of synergy of these two agents [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]
- To evaluate the use of FDG-PET as an early predictor of response to the combination of rapamycin and trastuzumab, be assessing changes in glucose
metabolism and cell viability between pre- and post-treatment [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]
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Same as current |
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A Phase II Study of Rapamycin and Trastuzumab for Patients With HER-2 Receptor Positive Metastatic Breast Cancer |
A Phase II Study of Rapamycin (Rapamune, Sirolimus) and Trastuzumab (Herceptin) for Patients With HER-2 Receptor Positive Metastatic Breast Cancer |
Rapamune (generic name: Sirolimus®) is a drug that has been approved by the Food and Drug Administration (government) for use in patients receiving a kidney transplant to prevent the patient's body from rejecting the transplanted kidney. It has shown antitumor effects in the laboratory, but has not been approved at this time for the treatment of cancer. Herceptin is a new form of chemotherapy that has been approved by the Food and Drug Administration for the treatment of breast cancer.
This study is designed to evaluate the effect and safety of combining Rapamune and Herceptin on breast cancer. Rapamune and Herceptin are being combined because results from our laboratory studies suggest that the combination of the two drugs is superior to either drug used alone. Results from laboratory studies performed at other institutions suggest that adding Rapamune to Herceptin may also reverse the resistance to Herceptin. Although there has been extensive experience using Herceptin alone and Rapamune alone in human subjects, the combination of Herceptin and Rapamune has not been previously evaluated. In addition, we hope to better understand how these treatments work against an individual woman's tumor by analyzing tissue samples before, and during treatment. |
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Phase II |
Interventional |
Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study |
Breast Cancer |
- Drug: Rapamycin
- Drug: Trastuzumab
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Recruiting |
30 |
May 2009 |
May 2009 (final data collection date for primary outcome measure) |
Inclusion Criteria:
Exclusion Criteria:
- Active infection or treatment for systemic infections within 14 days of enrollment
- Patients with active brain metastases requiring treatment, inclusive but not limited to surgery, radiation, and corticosteroids (patients with asymptomatic non- progressing brain metastasis who have completed treatment ≥30 days before enrollment and without evidence of progression on a post treatment MRI may be considered for the study).
- Pregnant or lactating women
- Prior chemotherapy within the last 4 weeks (last 6 weeks for nitrosureas/mitomycin)
- Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation).
- Prior therapy with rapamycin, rapamycin analogs, or experimental agents targeting mTOR.
- Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- Ejection fraction <50% or below the lower limit of the institutional normal range, whichever is lower
- Hypersensitivity to trial medications
- Patients may not be receiving any other investigational agents within 30 days before enrollment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because the investigational agents may have the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated.
- HIV-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents.
- Use of all herbal and alternative medications within 4 weeks. All herbal and alternative medications should be discontinued while on study, these include but not limited to: Hydrastis canadensis (goldenseal) - Uncaria tomentosa (cat's claw) - Echinacea angustifolia roots - trifolium pratense (wild cherry) - matricaria chamomila (chamomile) - Glycyrrhiza glabra (licorice) - dillapiol - naringenim.
- Use of any of these medications within 4 weeks; cyclosporine, diltiazen, ketoconazole, rifampin, fluconazole, delavirdine, nicardipine, pioglitazone, and sulfonamides, erythromycin, clarithromycin, itraconazole, erythromycin, metoclopramide, nevirapine, phenobarbital, phenytoin, indinavir, fosamprenavir, nefazadone, St Johns Wort.
- Consumption of grapefruit juice is prohibited during the study.
- Use of warfarin (Coumadin), immunosuppressive agents or chronic oral, intravenous or topical steroid
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Female |
18 Years and older |
No |
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United States |
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NCT00411788 |
Maysa Abu-Khalaf, M.D. Principal Investigator, Yale University School of Medicine |
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Yale University |
Genentech |
Principal Investigator: |
Maysa Abu-Khalaf, MD |
Yale University |
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Yale University |
December 2008 |