- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00068757
Lonafarnib, Trastuzumab, and Paclitaxel in Treating Patients With HER2/Neu-Overexpressing Stage IIIB, Stage IIIC, or Stage IV Breast Cancer
Phase I Study of Lonafarnib (SCH66336) in Combination With Herceptin Plus Paclitaxel in HER 2 NEU Overexpressing Breast Cancer
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining lonafarnib and trastuzumab with paclitaxel may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with trastuzumab and paclitaxel in treating patients with HER2/neu-overexpressing stage IIIB, stage IIIC, or stage IV breast cancer.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of lonafarnib in combination with trastuzumab (Herceptin®) and paclitaxel in patients with HER2/neu-overexpressing stage IIIB, IIIC, or IV breast cancer.
- Determine the qualitative and quantitative toxicity of this regimen in these patients.
Secondary
- Determine the pharmacokinetic profiles of these drugs in these patients.
- Correlate the pharmacodynamics with the pharmacokinetics of this regimen in these patients.
- Correlate the pharmacokinetics and pharmacodynamics of this regimen with observed toxicity in these patients.
- Determine the response to this regimen in patients with measurable disease.
OUTLINE: This is a nonrandomized, open-label, multicenter, dose-escalation study of lonafarnib.
- Course 1: Patients receive a loading dose of trastuzumab (Herceptin®) IV over 90 minutes on day 1 and over 30 minutes on days 8 and 15. Patients also receive paclitaxel IV over 3 hours on day 1.
- Course 2: Patients receive trastuzumab IV over 30 minutes on days 1, 8, and 15 and paclitaxel IV over 3 hours on day 2. Patients also receive oral lonafarnib twice daily on days 3-21.
- Course 3 and all subsequent courses: Patients receive oral lonafarnib twice daily on days 1-21; trastuzumab IV over 30 minutes on days 1, 8, and 15; and paclitaxel IV over 3 hours on day 1.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of lonafarnib 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.
Patients are followed every 8 weeks until disease progression.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
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Brussels, Belgien, 1000
- Institut Jules Bordet
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Paris, Frankreich, 75248
- Institut Curie Hopital
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Amsterdam, Niederlande, 1066 CX
- Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed breast cancer
- Stage IIIB, IIIC, or IV
HER2/neu overexpression
3+ by immunohistochemistry
- 2+ allowed if positive fluorescent in situ hybridization
Disease meets the following treatment criteria:
- Paclitaxel/trastuzumab (Herceptin®) may be appropriate therapy
- Anthracycline therapy is not a suitable approach
- No clinical signs of CNS involvement
Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Male or female
Menopausal status
- Not specified
Performance status
- ECOG 0-2 OR
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- Neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10.0 g/dL (6.2 mmol/L)
Hepatic
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase less than 2.5 times ULN (5 times ULN if liver metastases are present)
- AST and ALT less than 2.5 times ULN (5 times ULN if liver metastases are present)
Renal
- Creatinine clearance at least 40 mL/min
Cardiovascular
- Cardiac ejection fraction normal by MUGA
- QTc interval no greater than 440 msec
- No cardiac dysfunction
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for up to 3 months after study participation
- No concurrent severe/unstable systemic disease
- No infection
- No circumstances that would preclude study participation (e.g., alcoholism or substance abuse)
- No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 1 year since prior trastuzumab
- No concurrent prophylactic growth factors
Chemotherapy
- More than 1 year since prior paclitaxel
- More than 4 weeks since other prior chemotherapy
Endocrine therapy
- More than 1 day since prior hormonal therapy
- More than 2 days since prior high-dose chronic steroids
- More than 2 days since prior ethinyl estradiol
- No concurrent high-dose chronic steroids
- No concurrent ethinyl estradiol
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- Not specified
Other
More than 2 days since prior administration of and no concurrent CYP3A4 inducers or inhibitors, including any of the following:
- Gestodene
- Itraconazole
- Ketoconazole
- Cimetidine
- Erythromycin
- Carbamazepine
- Phenobarbital
- Phenytoin
- Rifampin
- Sulfinpyrazone
- No concurrent grapefruit juice
- No other concurrent anticancer agents
- No other concurrent investigational therapy
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Maskierung: Keine (Offenes Etikett)
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
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Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 2.0
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
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Translational research
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Klinisches Ansprechen gemäß RECIST-Kriterien
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Pharmacokinetics (PK) and pharmacodynamics (PD)
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Mitarbeiter und Ermittler
Ermittler
- Studienstuhl: Jan H. M. Schellens, MD, PhD, The Netherlands Cancer Institute
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Hautkrankheiten
- Neubildungen
- Neubildungen nach Standort
- Brusterkrankungen
- Neoplasien der Brust
- Molekulare Mechanismen der pharmakologischen Wirkung
- Enzym-Inhibitoren
- Antineoplastische Mittel
- Tubulin-Modulatoren
- Antimitotische Mittel
- Mitose-Modulatoren
- Antineoplastische Mittel, Phytogen
- Antineoplastische Mittel, immunologische
- Paclitaxel
- Trastuzumab
- Lonafarnib
Andere Studien-ID-Nummern
- EORTC-16023-10051
- SPRI-P01900
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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