- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01562873
Ruxolitinib in Patients With Breast Cancer
3. Januar 2017 aktualisiert von: Nancy Lin, MD, Dana-Farber Cancer Institute
Phase II Study of Ruxolitinib (INCB018424) in Patients With PSTAT3+ Breast Cancer
Ruxolitinib is a drug which blocks the Janus tyrosine Kinase (JAK) signaling pathway.
It is thought that this pathway might be important in certain types of breast cancer, and that blocking this pathway might lead to anti-cancer effects.
This study is testing the effects of ruxolitinib in patients with breast cancer.
Studienübersicht
Detaillierte Beschreibung
Objectives:
Primary
- The primary objective of this two-stage, phase II study is to estimate the objective response rate to ruxolitinib in patients with metastatic or unresectable locally advanced breast cancer which is pStat3+ and which has progressed on at least one line of chemotherapy for advanced disease, and/or has recurred within 12 months of completion of neoadjuvant/adjuvant chemotherapy.
Secondary
- To describe the toxicity profile
- To evaluate clinical benefit rate (CR + PR + SD >/= 24 weeks)
- To estimate progression-free and overall survival
Exploratory
- To explore whether baseline hs-CRP level higher than the group median is associated with objective response
- To explore whether baseline IL-6 level higher than the group median is associated with objective response
- To describe hs-CRP level over time, and to describe the proportion of patients with a) hs-CRP > 3mg/L at baseline, on treatment, and at time of progression, and b) hs-CRP > 1mg/L at baseline, on treatment, and at time of progression
- To describe IL-6 level over time, and to describe the proportion of patients with IL-6 level above the upper limit of normal at baseline, on treatment, and at time of progression
- To describe pStat3 status by IHC in baseline metastatic biopsies
- To describe pStat3 status by IHC in on-study biopsies
- To describe pStat3 status by IHC in the time of progression biopsy samples
- To characterize archival and metastatic biopsy samples using triple immunofluorescence for CD44, CD24, and pStat3
- To characterize archival and metastatic biopsy samples using a previously characterized pStat3 gene signature
- To characterize circulating tumor cells (CTCs) for CD44, CD24, and pStat3 at baseline and time of progression
Studientyp
Interventionell
Einschreibung (Tatsächlich)
21
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Massachusetts
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Boston, Massachusetts, Vereinigte Staaten, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Vereinigte Staaten, 02114
- Massachusetts General Hospital
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
- Histologically or cytologically confirmed invasive breast cancer
- Must have known ER, PR and HER2 status
- Either, Triple Negative Metastatic Breast Cancer or
- Inflammatory Breast Cancer with any ER, PR HER2 status
- Availability of archival tissue specimen suitable for pStat3 testing
- Life expectancy of greater than 3 months
- Measurable disease by RECIST
- At least one prior chemotherapy regimen for treatment of metastatic breast cancer and/or recurrence within 12 months of completion of neoadjuvant/adjuvant chemotherapy or
- For patients with inflammatory breast cancer but no distant metastases, progression through standard neoadjuvant chemotherapy is required
Exclusion Criteria:
- Pregnant or breastfeeding
- Active brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib
- Clinically significant malabsorption syndrome
- Concurrent use of medications/substances that are strong inhibitors of CY3A4
- No uncontrolled intercurrent illness
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: Ruxolitinib-Cohort A
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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Andere Namen:
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Experimental: Ruxolitinib-Cohort B
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Objective Response Rate
Zeitfenster: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Clinical Benefit Rate
Zeitfenster: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Clinical benefit rate (CBR) was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions.
Stable disease (SD) is defined as any condition not meeting the above criteria.
SD needed to be a minimum 24 weeks in duration.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Overall Survival
Zeitfenster: In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
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In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-Free Survival
Zeitfenster: Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death.
Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.
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Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. Juni 2012
Primärer Abschluss (Tatsächlich)
1. Juni 2015
Studienabschluss (Tatsächlich)
1. Juni 2016
Studienanmeldedaten
Zuerst eingereicht
20. März 2012
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
22. März 2012
Zuerst gepostet (Schätzen)
26. März 2012
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
23. Februar 2017
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
3. Januar 2017
Zuletzt verifiziert
1. Januar 2017
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 12-024
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
NEIN
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