Liposomal Doxorubicin Before Mastectomy in Treating Women With Invasive Breast Cancer
A Phase I Study Assessing the Feasibility and Safety of Intraductal Administration of Pegylated Liposomal Doxorubicin (Doxil) in Women With Breast Cancer
RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy in different ways, such as into the breast ducts, may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase I trial is studying the side effects and best dose of liposomal doxorubicin when given before mastectomy in treating women with invasive breast cancer.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
OBJECTIVES:
Primary
- Evaluate the feasibility, safety, and maximum tolerated dose of intraductal pegylated doxorubicin HCl liposome in women with invasive breast cancer awaiting mastectomy.
Secondary
- Determine the pharmacokinetics of intraductal pegylated doxorubicin HCl liposome, including serial plasma concentrations of doxorubicin and doxorubicinol and tissue concentrations in different portions of the breast at the time of surgery.
OUTLINE: This is a dose-escalation study.
Patients receive an intraductal injection of pegylated doxorubicin HCl liposome* on day 1. Patients undergo mastectomy 2-4 weeks later.
Cohorts of 3-6 patients receive escalating doses of pegylated doxorubicin HCl liposome* until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
NOTE: *The first cohort of 3 patients receive intraductal dextrose only followed by surgery as a feasibility study. An additional 3 patients receiving intravenous PLD will be enrolled in a pharmacokinetic control portion of the study.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
-
-
Indiana
-
Indianapolis, Indiana, Spojené státy, 46202-5289
- Indiana University Melvin and Bren Simon Cancer Center
-
-
Maryland
-
Baltimore, Maryland, Spojené státy, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
DISEASE CHARACTERISTICS:
Histologically confirmed infiltrating carcinoma of the breast meeting any of the following criteria:
- T1-3, any N disease
- Proven ductal carcinoma in situ
Unresected disease
Planned mastectomy as definitive surgical procedure
- Known or suspected metastatic disease allowed provided mastectomy is planned
- Nonpalpable tumor allowed (e.g., initial T2-3 tumor that responded to preoperative therapy)
- No inflammatory breast cancer or other T4 features
Successful baseline ductogram
- Baseline nipple aspiration procedure must identify a duct productive of nipple aspirate fluid
- No severe nipple retraction
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- Female patients
- Menopausal status not specified
- ECOG performance status 0-2
- Absolute neutrophil count ≥1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Creatinine ≤ 2 times upper limit of normal (ULN)
- Bilirubin ≤ 2 times ULN
- AST and ALT ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No significant history of severe allergy to iodinated contrast material or debilitating anxiety that may not allow for a ductogram
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior preoperative chemotherapy, trastuzumab (Herceptin®), or hormonal therapy allowed provided it was completed 7-14 days prior to study treatment
- No prior radiation therapy, excisional biopsy, breast reduction, areolar surgery, or breast implant (present or past history of implant that was removed)
- No other prior procedure that may have altered the breast ductal system in the ipsilateral breast
- No other concurrent chemotherapy, radiotherapy, endocrine therapy, or biologic agents for breast cancer
- No other concurrent investigational drugs
- Concurrent bisphosphonates allowed
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Intraductal arm
Participants received intraductal administration of dextrose or dextrose with pegylated liposomal doxorubicin hydrochloride (or PLD) prior to conventional surgery for breast cancer.
|
Patients will receive PLD intraductally according to the dose escalation schema (Dose Level -1=1 mg, Dose Level 1=2 mg, Dose Level 2= 5mg, Dose Level 3=10 mg).
The PLD dose will be diluted in 5% dextrose in water and will be mixed for a total volume of 5 ml.
The PLD will be administered via a breast duct (i.e., intraductally) using a microcatheter
Ostatní jména:
|
|
Aktivní komparátor: Intravenous arm
Participants receiving standard intravenous administration of pegylated liposomal doxorubicin prior to breast biopsy for drug concentrations.
|
Blood samples and a breast tissue biopsy collected to look at levels of doxorubincol from patients receiving intravenous pegylated liposomal doxorubin to compare to the group receiving drug intraductally.
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Maximum Tolerated Dose (MTD)
Časové okno: Until up to 30 days after PLD administration
|
Maximum tolerated dose (MTD) of administering pegylated liposomal doxorubicin (PLD) into one duct of women with breast cancer awaiting mastectomy.
MTD reflects highest dose of drug that did not cause Dose Limiting Toxicity (DLT) in more than 30% of patients.
|
Until up to 30 days after PLD administration
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Concentrations of Doxorubicin in Blood (Plasma) at Definitive Surgery
Časové okno: Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery/biopsy
|
Due to the limited number of samples and detectable levels, the maximum concentration of doxorubicin in blood (plasma) across all the participants in each group is reported.
|
Baseline, 4 hrs, day2/24 hrs, day 8, day of surgery/biopsy
|
|
Concentrations of Doxorubicin in Tissue at Definitive Surgery
Časové okno: Day of surgery/biopsy
|
Due to the limited number of samples and detectable levels, the maximum concentration of doxorubicin in tissue across all the participants in each group is reported.
|
Day of surgery/biopsy
|
Spolupracovníci a vyšetřovatelé
Spolupracovníci
Vyšetřovatelé
- Studijní židle: Vered Stearns, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- J0503 CDR0000459502
- P30CA006973 (Grant/smlouva NIH USA)
- JHOC-J0503 (Jiný identifikátor: SKCCC at Johns Hopkins)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .