Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
7 sierpnia 2018 zaktualizowane przez: 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.
Przegląd badań
Typ studiów
Interwencyjne
Zapisy (Rzeczywisty)
105
Faza
- Faza 2
- Faza 1
Kontakty i lokalizacje
Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.
Lokalizacje studiów
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Queensland
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South Brisbane, Queensland, Australia, 4101
- Mater Private Centre for HOCA
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Victoria
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Wodonga, Victoria, Australia, 3690
- Border Medical Oncology
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RS
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Porto Alegre, RS, Brazylia, 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, Brazylia, 98700-000
- Associacao Hospital de Caridade Ijui
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Beijing, Chiny, 100071
- The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
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Beijing
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Beijing, Beijing, Chiny, 100021
- Cancer Hospital, Chinese Academy of Medical Sciences
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Beijing, Beijing, Chiny, 100032
- Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
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Jiangsu
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Nanjing, Jiangsu, Chiny, 210009
- Jiangsu Cancer Hospital
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Zagreb, Chorwacja, 10000
- University Hospital Center Zagreb Department of Oncology
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Kazan, Federacja Rosyjska, 420029
- Republican Clinical Oncology Dispensary
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Perm, Federacja Rosyjska, 614066
- GUZ Perm Regional Oncology Dispensary
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Saint Petersburg, Federacja Rosyjska, 197022
- GUZ City Clinical Oncology Dispensary
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Saint Petersburg, Federacja Rosyjska, 188663
- Leningrad Regional Oncology Dispensary
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Saint Petersburg, Federacja Rosyjska, 197022
- Saint-Petersburg State Medical University n.a. acad. I.P. Pavlov, Laboratory of Thoracic Oncology of Pulmonology Research Institute
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Barcelona, Hiszpania, 08035
- Hospital Vall d'hebrón
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Madrid, Hiszpania, 28040
- Hospital Clinico San Carlos
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Madrid, Hiszpania, 28007
- Hospital Gregorio Marañón
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Valencia, Hiszpania, 46010
- Hospital Clínico Universitario de Valencia
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Hong Kong, Hongkong
- UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
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Seoul, Republika Korei, 120-752
- Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine
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Seoul, Republika Korei, 135-710
- Department of Hematology/Oncology, Samsung Medical Center
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Seoul, Republika Korei, 138-736
- Asan Medical Center Department of Medicine Division of Oncology
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Singapore, Singapur, 308433
- Johns Hopkins Singapore International Medical Centre
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Alabama
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Mobile, Alabama, Stany Zjednoczone, 36604
- USA Mitchell Cancer Institute
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California
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Long Beach, California, Stany Zjednoczone, 90813
- Pacific Shores Medical Group
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Los Angeles, California, Stany Zjednoczone, 90033
- University of Southern California
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Florida
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Orlando, Florida, Stany Zjednoczone, 32804
- Florida Hospital Cancer Institute
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Idaho
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Post Falls, Idaho, Stany Zjednoczone, 83854
- Kootenai Cancer Center
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Indiana
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Lafayette, Indiana, Stany Zjednoczone, 47905
- The Care Group, LLC. dba Horizon Oncology Center
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Missouri
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Saint Louis, Missouri, Stany Zjednoczone, 63110
- Washington University School of Medicine Siteman Cancer Center
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New York
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Lake Success, New York, Stany Zjednoczone, 11042
- Arena Oncology Associates, PC
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Ohio
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Dayton, Ohio, Stany Zjednoczone, 45420
- Dayton Clinical Oncology Program
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Pennsylvania
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West Reading, Pennsylvania, Stany Zjednoczone, 19611
- Berks Hematology Oncology
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Texas
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Richardson, Texas, Stany Zjednoczone, 75080
- HOPE Oncology
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San Antonio, Texas, Stany Zjednoczone, 78229
- Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development
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Budapest, Węgry, 1122
- Országos Onkológiai Intézet "B" Belgyogyaszati osztaly
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Nyiregyhaza, Węgry, 4400
- Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
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Kryteria uczestnictwa
Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.
Kryteria kwalifikacji
Wiek uprawniający do nauki
18 lat i starsze (Dorosły, Starszy dorosły)
Akceptuje zdrowych ochotników
Nie
Płeć kwalifikująca się do nauki
Wszystko
Opis
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.
Plan studiów
Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nielosowe
- Model interwencyjny: Zadanie sekwencyjne
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
|---|---|
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Eksperymentalny: Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Inne nazwy:
Capecitabine orally on days 1-14 of each 21 day cycle
Inne nazwy:
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Eksperymentalny: Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Inne nazwy:
Capecitabine orally on days 1-14 of each 21 day cycle
Inne nazwy:
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Eksperymentalny: Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Inne nazwy:
Capecitabine orally on days 1-14 of each 21 day cycle
Inne nazwy:
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Eksperymentalny: Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Inne nazwy:
Capecitabine orally on days 1-14 of each 21 day cycle
Inne nazwy:
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Eksperymentalny: Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Inne nazwy:
Capecitabine orally on days 1-14 of each 21 day cycle
Inne nazwy:
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Eksperymentalny: 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
Inne nazwy:
Capecitabine orally on days 1-14 of each 21 day cycle
Inne nazwy:
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Eksperymentalny: 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
Inne nazwy:
Capecitabine orally on days 1-14 of each 21 day cycle
Inne nazwy:
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Number of Participants With Dose Limiting Toxicities
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Overall Response Rate
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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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Współpracownicy i badacze
Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.
Sponsor
Publikacje i pomocne linki
Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.
Daty zapisu na studia
Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
9 grudnia 2008
Zakończenie podstawowe (Rzeczywisty)
1 listopada 2010
Ukończenie studiów (Rzeczywisty)
1 czerwca 2018
Daty rejestracji na studia
Pierwszy przesłany
22 sierpnia 2008
Pierwszy przesłany, który spełnia kryteria kontroli jakości
22 sierpnia 2008
Pierwszy wysłany (Oszacować)
26 sierpnia 2008
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
5 września 2018
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
7 sierpnia 2018
Ostatnia weryfikacja
1 sierpnia 2018
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- 3144A1-2206 / B1891017
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Tak
Bada produkt urządzenia regulowany przez amerykańską FDA
Nie
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .