Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
7. August 2018 aktualisiert von: Puma Biotechnology, Inc.
A Phase 1/2, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Subjects With Solid Tumors And ErbB-2 Positive Metastatic Or Locally Advanced Breast Cancer
This is a world wide phase 1/2, open-label, study of neratinib in combination with capecitabine, conducted in 2 parts.
In Part 1, 3 to 9 subjects with solid tumors will be enrolled in each dose group of the combination of neratinib and capecitabine. Each subject will participate in only 1 dose group.
Additional subjects may be included at any dose level to further assess the safety and tolerability at that dose level.
In Part 2, up to 60 subjects with erbB-2 positive metastatic breast cancer will receive treatment with the combination of neratinib and capecitabine at the maximum tolerated dose level, as determined in Part 1. In addition 20 subjects with prior lapatinib exposure will be enrolled in Part 2.
Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted, if appropriate. In case one test article of the combination is discontinued due to intolerance the other test article can be administered alone.
The primary objectives of Part 1 are to assess the safety and tolerability, and to define the maximum tolerated dose (MTD) of neratinib in combination with capecitabine in subjects with advanced solid tumors.
The primary objective of Part 2 of this study is to confirm the MTD determined in Part 1.
The secondary objective of Part 1 is to collect information on preliminary anti-tumor activity of the combination of neratinib and capecitabine.
Secondary objectives for Part 2 are to collect pharmacokinetic information and to obtain additional efficacy data, such as Objective Response Rate, for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
105
Phase
- Phase 2
- Phase 1
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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Queensland
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South Brisbane, Queensland, Australien, 4101
- Mater Private Centre for HOCA
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Victoria
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Wodonga, Victoria, Australien, 3690
- Border Medical Oncology
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RS
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Porto Alegre, RS, Brasilien, 90035-001
- Associacao Hospitalar Moinhos de Vento Instituto de Edicacao e Pesquisa
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RS - Brazil
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Ijui, RS - Brazil, Brasilien, 98700-000
- Associacao Hospital de Caridade Ijui
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Beijing, China, 100071
- The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
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Beijing
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Beijing, Beijing, China, 100021
- Cancer Hospital, Chinese Academy of Medical Sciences
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Beijing, Beijing, China, 100032
- Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
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Jiangsu
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Nanjing, Jiangsu, China, 210009
- Jiangsu Cancer Hospital
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Hong Kong, Hongkong
- UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
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Seoul, Korea, Republik von, 120-752
- Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine
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Seoul, Korea, Republik von, 135-710
- Department of Hematology/Oncology, Samsung Medical Center
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Seoul, Korea, Republik von, 138-736
- Asan Medical Center Department of Medicine Division of Oncology
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Zagreb, Kroatien, 10000
- University Hospital Center Zagreb Department of Oncology
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Kazan, Russische Föderation, 420029
- Republican Clinical Oncology Dispensary
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Perm, Russische Föderation, 614066
- GUZ Perm Regional Oncology Dispensary
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Saint Petersburg, Russische Föderation, 197022
- GUZ City Clinical Oncology Dispensary
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Saint Petersburg, Russische Föderation, 188663
- Leningrad Regional Oncology Dispensary
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Saint Petersburg, Russische Föderation, 197022
- Saint-Petersburg State Medical University n.a. acad. I.P. Pavlov, Laboratory of Thoracic Oncology of Pulmonology Research Institute
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Singapore, Singapur, 308433
- Johns Hopkins Singapore International Medical Centre
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Barcelona, Spanien, 08035
- Hospital Vall d'hebrón
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Madrid, Spanien, 28040
- Hospital Clinico San Carlos
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Madrid, Spanien, 28007
- Hospital Gregorio Marañón
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Valencia, Spanien, 46010
- Hospital Clínico Universitario de Valencia
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Budapest, Ungarn, 1122
- Országos Onkológiai Intézet "B" Belgyogyaszati osztaly
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Nyiregyhaza, Ungarn, 4400
- Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
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Alabama
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Mobile, Alabama, Vereinigte Staaten, 36604
- USA Mitchell Cancer Institute
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California
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Long Beach, California, Vereinigte Staaten, 90813
- Pacific Shores Medical Group
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Los Angeles, California, Vereinigte Staaten, 90033
- University of Southern California
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Florida
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Orlando, Florida, Vereinigte Staaten, 32804
- Florida Hospital Cancer Institute
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Idaho
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Post Falls, Idaho, Vereinigte Staaten, 83854
- Kootenai Cancer Center
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Indiana
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Lafayette, Indiana, Vereinigte Staaten, 47905
- The Care Group, LLC. dba Horizon Oncology Center
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Missouri
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Saint Louis, Missouri, Vereinigte Staaten, 63110
- Washington University School of Medicine Siteman Cancer Center
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New York
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Lake Success, New York, Vereinigte Staaten, 11042
- Arena Oncology Associates, PC
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Ohio
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Dayton, Ohio, Vereinigte Staaten, 45420
- Dayton Clinical Oncology Program
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Pennsylvania
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West Reading, Pennsylvania, Vereinigte Staaten, 19611
- Berks Hematology Oncology
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Texas
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Richardson, Texas, Vereinigte Staaten, 75080
- HOPE Oncology
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San Antonio, Texas, Vereinigte Staaten, 78229
- Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development
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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
PART 1:
- confirmed pathologic diagnosis of a solid tumor not curable with available therapies for which neratinib plus capecitabine is a reasonable treatment option.
PART 2:
- confirmed histologically and/or cytologically confirmed diagnosis of breast cancer, metastatic or locally advanced.
- erbB-2 gene amplified tumor (FISH or CISH) or erbB-2 overexpression (IHC 3+, or IHC2+ with FISH or CISH confirmation), based on local testing, or based on centralized FISH testing prior to day 1.
- disease progression on or following at least 1 prior trastuzumab containing treatment regimen (at least 6 weeks) for metastatic or locally advanced disease. (Prior adjuvant trastuzumab is allowed but not required). A 2 week period is required between the last dose of trastuzumab treatment and first dose of the test article.
- Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, and/or metastatic disease treatment setting.
PARTS 1 and 2:
- At least 1 measurable lesion as defined by RECIST criteria.
- LVEF within institutional range of normal as measured by multi-gated acquisition (MUGA) or echocardiogram (ECHO).
EXCLUSION CRITERIA
PART 2:
- prior treatment with capecitabine, lapatinib (20 subjects with prior lapatinib exposure will be enrolled) or any erbB-2 targeted agents except trastuzumab. Treatment with erbB-2 targeted therapy must exceed 2 weeks (14 days) in order to be exclusionary.
- prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m², epirubicin dose of greater than 800 mg/m², or the equivalent dose for other anthracyclines.
PARTS 1 and 2:
- Subjects with bone as the only site of disease.
- Active uncontrolled or symptomatic central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Subjects with a history of CNS metastases or cord compression are allowable if they have been considered definitively treated and are off anticonvulsants and steroids for at least 4 weeks before the first dose of test article.
- Any other cancer within 5 years prior to screening with the exception of adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
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: Sequenzielle Zuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Andere Namen:
Capecitabine orally on days 1-14 of each 21 day cycle
Andere Namen:
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Experimental: Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Andere Namen:
Capecitabine orally on days 1-14 of each 21 day cycle
Andere Namen:
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Experimental: Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Andere Namen:
Capecitabine orally on days 1-14 of each 21 day cycle
Andere Namen:
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Experimental: Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Andere Namen:
Capecitabine orally on days 1-14 of each 21 day cycle
Andere Namen:
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Experimental: Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Andere Namen:
Capecitabine orally on days 1-14 of each 21 day cycle
Andere Namen:
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Experimental: Neratinib and Capecitabine MTD (Dose Group 6)
Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib
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Neratinib orally once daily continually
Andere Namen:
Capecitabine orally on days 1-14 of each 21 day cycle
Andere Namen:
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Experimental: Neratinib and Capecitabine MTD (Dose Group 7)
Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib
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Neratinib orally once daily continually
Andere Namen:
Capecitabine orally on days 1-14 of each 21 day cycle
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Number of Participants With Dose Limiting Toxicities
Zeitfenster: From first dose date to day 21
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Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).
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From first dose date to day 21
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Maximum Tolerated Dose (MTD) of Neratinib
Zeitfenster: From first dose date to day 21.
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MTD reflects the highest dose of neratinib plus capeciteabine that did not cause a selected Grade 3 toxicity in >= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting >3 days, 2) Grade 3 diarrhea lasting >2 days on optimal medical therapy or associated with fever or dehydration.
3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery [to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
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From first dose date to day 21.
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Maximum Tolerated Dose (MTD) of Capecitabine
Zeitfenster: From first dose date to day 21.
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MTD reflects the highest dose of capecitabine in combination with neratinib that did not cause a selected Grade 3 toxicity in >= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting >3 days, 2) Grade 3 diarrhea lasting >2 days on optimal medical therapy or associated with fever or dehydration.
3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery [to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
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From first dose date to day 21.
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Overall Response Rate
Zeitfenster: From first dose date to progression or last tumor assessment, up to three years.
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Number of Subjects with Complete or Partial Response 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.
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From first dose date to progression or last tumor assessment, up to three years.
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Clinical Benefit Rate
Zeitfenster: From first dose date to progression or last tumor assessment, up to three years.
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The percentage of subjects with Complete Response, Partial Response, or Stable Disease at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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From first dose date to progression or last tumor assessment, up to three years.
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Duration of Response
Zeitfenster: From start date of response to first PD/death, up to three years.
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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 of recurrence or progressive disease (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
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From start date of response to first PD/death, up to three years.
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
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 (Tatsächlich)
9. Dezember 2008
Primärer Abschluss (Tatsächlich)
1. November 2010
Studienabschluss (Tatsächlich)
1. Juni 2018
Studienanmeldedaten
Zuerst eingereicht
22. August 2008
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
22. August 2008
Zuerst gepostet (Schätzen)
26. August 2008
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
5. September 2018
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
7. August 2018
Zuletzt verifiziert
1. August 2018
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 3144A1-2206 / B1891017
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Ja
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
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