Neoadjuvant Tipifarnib, Docetaxel, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Stage IIIA or Stage IIIB Breast Cancer
Phase Ib/II Neoadjuvant Trial of the Farnesyltransferase Inhibitor, R115777 With Docetaxel and Capecitabine for Patients With Stage IIIA or IIIB Breast Cancer
Studienübersicht
Status
Bedingungen
Detaillierte Beschreibung
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and recommended dose of capecitabine in combination with docetaxel and tipifarnib in patients with locally advanced or metastatic solid tumors. (Phase Ib) II. Determine the complete pathological and clinical response rate in patients with stage IIIA or IIIB breast cancer treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. II. Determine disease-free and overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of capecitabine. Patients in phase II are stratified according to type of breast cancer (inflammatory vs noninflammatory).
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine 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.
Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine. Patients in phase Ib are followed at 3 months.
Patients in phase II are followed every 4 months for up to 5 years.
PROJECTED ACCRUAL: A total of 24-53 patients (9-18 for phase Ib and 15-35 for phase II) will be accrued for this study within 14-35 months.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienorte
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Arizona
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Scottsdale, Arizona, Vereinigte Staaten, 85259
- Mayo Clinic in Arizona
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District of Columbia
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Washington, District of Columbia, Vereinigte Staaten, 20060
- Howard University Cancer Center CCOP
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Florida
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Jacksonville, Florida, Vereinigte Staaten, 32224-9980
- Mayo Clinic in Florida
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Michigan
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Detroit, Michigan, Vereinigte Staaten, 48201
- Barbara Ann Karmanos Cancer Institute
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Minnesota
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Rochester, Minnesota, Vereinigte Staaten, 55905
- Mayo Clinic
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Missouri
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Saint Louis, Missouri, Vereinigte Staaten, 63110
- Washington University School of Medicine
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Wisconsin
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Milwaukee, Wisconsin, Vereinigte Staaten, 53201
- University of Wisconsin Medical School
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
Histologically or cytologically confirmed solid tumor
- Locally advanced or metastatic
- No known standard therapy that is potentially curative or definitely capable of extending life expectancy
No history of metastatic brain disease within the past 6 months
- Treated metastatic brain disease is allowed provided disease has been stable for more than 6 months and does not require concurrent steroids or anti-seizure medication
Histologically confirmed breast cancer
- Stage IIIA or stage IIIB, including ipsilateral palpable supraclavicular lymph node(s) without other distant metastasis
Invasive disease confirmed by 1 of the following*:
- Incisional biopsy
- Punch biopsy (applicable for clinical T4b tumors)
- Core needle (cutting needle) biopsies
- No distant metastatic disease
Hormone receptor status:
- Not specified
- Male or female
- Performance status - ECOG 0-1
- Absolute neutrophil count at least 2,000/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10.0 g/dL
- Bilirubin no greater than upper limit of normal (ULN)
- Alkaline phosphatase no greater than 2.5 times ULN
- AST no greater than 2.5 times ULN
- Creatinine no greater than 1.25 times ULN
- Creatinine clearance at least 50 mL/min
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection requiring antibiotics
- No diabetes
- No symptomatic neurologic condition
- No other uncontrolled serious medical condition
- No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- No history of hypersensitivity to intravenous paclitaxel or other medication containing Cremophor EL or polysorbate 80 as a carrier (phase Ib)
Phase Ib only:
- More than 4 weeks since prior immunotherapy
- More than 4 weeks since prior biologic therapy
- No concurrent immunotherapy
Phase Ib and II:
- No concurrent prophylactic filgrastim (G-CSF)
Phase Ib only:
- More than 1 year since prior adjuvant docetaxel before metastatic relapse
- More than 4 weeks since prior chemotherapy and recovered
No prior capecitabine AND docetaxel (in combination or as single agents)
- Prior capecitabine OR docetaxel allowed
- No other concurrent chemotherapy
Phase II only:
- No prior cytotoxic chemotherapy for breast cancer
Phase Ib only:
- More than 3 weeks since prior radiotherapy
- No prior radiotherapy to more than 25% of bone marrow
- No concurrent radiotherapy
Phase II only:
- No prior radiotherapy for breast cancer
Phase Ib only:
- More than 4 weeks since prior major surgery
Phase II only:
- No prior surgery (other than core or incisional biopsy for diagnostic purposes) for breast cancer
Phase Ib only:
- No other ancillary investigational therapy
Phase Ib and II:
- No concurrent sorivudine or brivudine
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: Treatment (tipifarnib, capecitabine, docetaxel)
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48 hours after completion of the initial dose of tipifarnib, patients receive treatment as in phase Ib for up to 6 courses at the MTD of capecitabine. |
Korrelative Studien
Korrelative Studien
Gegeben IV
Andere Namen:
PO gegeben
Andere Namen:
Given orally (PO)
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I)
Zeitfenster: 21 days
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21 days
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Pathologic complete response rate (Phase II)
Zeitfenster: Up to 5 years
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Estimated by the number of patients with a complete pathologic response divided by the total number of evaluable patients.
Ninety-five percent confidence intervals for the true pathologic complete response probability will be calculated according to the approach of Duffy and Santner.
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Up to 5 years
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Clinical tumor response (complete response [CR] or partial response [PR]) (Phase I)
Zeitfenster: Up to 5 years
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Clinical responses will be summarized by simple descriptive summary statistics.
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Up to 5 years
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Overall survival
Zeitfenster: From registration to death due to any cause, assessed up to 5 years
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The distribution of survival time will be estimated using the method of Kaplan-Meier.
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From registration to death due to any cause, assessed up to 5 years
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Toxicity as assessed by the National Cancer Institute (NCI) CTCAE version 3.0
Zeitfenster: Up to 5 years
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Up to 5 years
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Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Philip Philip, Mayo Clinic
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (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
Zusätzliche relevante MeSH-Bedingungen
- Hautkrankheiten
- Neubildungen nach histologischem Typ
- Neubildungen
- Neubildungen nach Standort
- Neubildungen, Drüsen und Epithelien
- Brusterkrankungen
- Neoplasien der Brust
- Karzinom
- Entzündliche Neoplasmen der Brust
- Brustneoplasmen, männlich
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Tubulin-Modulatoren
- Antimitotische Mittel
- Mitose-Modulatoren
- Docetaxel
- Capecitabin
- Tipifarnib
Andere Studien-ID-Nummern
- NCI-2012-01442 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
- P30CA015083 (US NIH Stipendium/Vertrag)
- N01CM62205 (US NIH Stipendium/Vertrag)
- WSU-C-2679
- MAYO-MC0131
- NCI-5599
- CDR0000331694
- MC0131 (Andere Kennung: Mayo Clinic)
- 5599 (Andere Kennung: CTEP)
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