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A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer

26 juni 2018 uppdaterad av: Puma Biotechnology, Inc.

A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer

The purpose of this study is to determine the safety and efficacy of HKI-272 (neratinib) in combination with trastuzumab in patients with advanced breast cancer.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

Open label phase 1/2 study of ascending multiple oral doses of HKI-272 in combination with IV trastuzumab in subjects with advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Three to six subjects will be enrolled in each dose group. Adverse events and dose limiting toxicities will be assessed from the first dose of study drug though day 21. When the maximum tolerated dose (MTD) of HKI-272 plus trastuzumab is determined, an additional 30 subjects will be enrolled at that dose level, and followed for progression free survival for approximately 1 year.

Studietyp

Interventionell

Inskrivning (Faktisk)

45

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Frankrike
      • Paris, Frankrike, 75005
        • Institut Curie
      • Saint-Herblain, Frankrike, 44805
        • Centre Rene Gauducheau
  • Förenta staterna
    • California
      • Duarte, California, Förenta staterna, 91010-3000
        • City of Hope National Medical Center
      • Los Angeles, California, Förenta staterna, 90033
        • LAC/USC Medical Center, USC/Norris Comprehensive Cancer Center
      • Pasadena, California, Förenta staterna, 91105
        • City of Hope National Medical Center
    • Maryland
      • Baltimore, Maryland, Förenta staterna, 21201
        • University of Maryland, University of Maryland Medical Center
    • North Carolina
      • Durham, North Carolina, Förenta staterna, 27710
        • Duke University, Duke University Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Förenta staterna, 19111
        • Fox Chase Cancer Center
  • Kina
      • Beijing, Kina, 100853
        • Chinese PLA General Hospital
      • Beijing, Kina, 100021
        • Cancer Hospital, Academy of Med Science and Peking Union Med
      • Beijing, Kina, 100071
        • 307 Hospital of Chinese People's Liberation Army
    • Jiangsu
      • Nanjing, Jiangsu, Kina, 210002
        • Chinese Nanjing Bayi Hospital
    • Tianjin
      • Tianjin, Tianjin, Kina, 300121
        • Tianjin Union Medicine Center
  • Schweiz
      • Lausanne, Schweiz, CH-1011
        • Centre Hospitalier Universitaire Vaudois

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy
  • Progression following at least one Herceptin-containing cytotoxic chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting)
  • HER2 positive breast cancer
  • At least one measurable target lesion
  • Adequate performance status
  • Adequate cardiac, kidney, and liver function
  • Adequate blood counts
  • Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control

Exclusion Criteria:

  • More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease
  • Major surgery, chemotherapy, radiotherapy, investigational agents, Herceptin or other cancer therapy within 2 weeks of treatment day 1
  • Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
  • Extensive visceral disease
  • Active central nervous system metastases
  • Pregnant or breast feeding women
  • Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom
  • Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)
  • Significant cardiac disease or dysfunction
  • History of life-threatening hypersensitivity to Herceptin
  • Inability or unwillingness to swallow HKI-272 capsules
  • Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Part 1 - dose level 1 (160 mg)
All subjects receiving HKI-272 dose level 1 in combination with trastuzumab
Läkemedel: HKI-272
HKI-272 by mouth
Andra namn:
  • neratinib
Läkemedel: trastuzumab
trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
Andra namn:
  • Herceptin
Experimentell: Part 1 - dose level 2 (240 mg)
All subjects receiving HKI-272 dose level 2 in combination with trastuzumab
Läkemedel: HKI-272
HKI-272 by mouth
Andra namn:
  • neratinib
Läkemedel: trastuzumab
trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
Andra namn:
  • Herceptin
Experimentell: Part 2 - expanded MTD cohort
All subjects receiving HKI-272 in combination with trastuzumab
Läkemedel: HKI-272
HKI-272 by mouth
Andra namn:
  • neratinib
Läkemedel: trastuzumab
trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter
Andra namn:
  • Herceptin

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
16-week Progression-free Survival (PFS) Rate
Tidsram: From first dose date to progression status (PD or death) at 16-week
16-week progression-free survival (PFS) rate for subjects with advanced breast cancer who receive neratinib at the maximum tolerated dose (MTD) in combination with trastuzumab, evaluable population.
From first dose date to progression status (PD or death) at 16-week

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Objective Response Rate (ORR)
Tidsram: From first dose date to progression or last tumor assessment, up to five and a half years.
Percentage of participants with partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
From first dose date to progression or last tumor assessment, up to five and a half years.
Duration of Response (DOR)
Tidsram: From start date of response to first PD, assessed up to five and half years after the first subject was randomized
Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date on which recurrence or PD was objectively documented, taking as the reference for PD the smallest measurements recorded since the test article administration started.
From start date of response to first PD, assessed up to five and half years after the first subject was randomized
Progression Free Survival (PFS)
Tidsram: From first dose date to progression or death, assessed up to five and half years.
Progression Free Survival was measured from the date of the first dose of test article until the first date on which recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment.
From first dose date to progression or death, assessed up to five and half years.
Clinical Benefit Rate (CBR)
Tidsram: From first dose date to progression or last tumor assessment, assessed up to five and half years.
The percentage of participants with a best overall response of a complete response (CR) or partial response (PR) or stable disease (SD) >=24 weeks.
From first dose date to progression or last tumor assessment, assessed up to five and half years.
Area Under the Curve of Neratinib Concentration
Tidsram: Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.
Area Under the Curve of Neratinib concentration at day 22 following Administration of Neratinib 240 mg in combination with Trastuzumab 2 mg/kg in Subjects with Cancer.
Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.
Terminal-phase Elimination Half-life of Neratinib in Combination With Trastuzumab.
Tidsram: Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6
Terminal-phase elimination half-life of Neratinib at day 22 following Administration of Neratinib 240 mg in combination with Trastuzumab 2 mg/kg to Subjects with Cancer.
Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Puma Biotechnology, Inc.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

4 april 2007

Primärt slutförande (Faktisk)

31 juli 2009

Avslutad studie (Faktisk)

2 mars 2018

Studieregistreringsdatum

Först inskickad

9 november 2006

Först inskickad som uppfyllde QC-kriterierna

9 november 2006

Första postat (Uppskatta)

10 november 2006

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

24 juli 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

26 juni 2018

Senast verifierad

1 juni 2018

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • 3144A1-202 / B1891013

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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