Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
7. srpna 2018 aktualizováno: 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.
Přehled studie
Typ studie
Intervenční
Zápis (Aktuální)
105
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Queensland
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South Brisbane, Queensland, Austrálie, 4101
- Mater Private Centre for HOCA
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Victoria
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Wodonga, Victoria, Austrálie, 3690
- Border Medical Oncology
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RS
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Porto Alegre, RS, Brazílie, 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, Brazílie, 98700-000
- Associacao Hospital de Caridade Ijui
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Zagreb, Chorvatsko, 10000
- University Hospital Center Zagreb Department of Oncology
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Hong Kong, Hongkong
- UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
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Seoul, Korejská republika, 120-752
- Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine
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Seoul, Korejská republika, 135-710
- Department of Hematology/Oncology, Samsung Medical Center
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Seoul, Korejská republika, 138-736
- Asan Medical Center Department of Medicine Division of Oncology
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Budapest, Maďarsko, 1122
- Országos Onkológiai Intézet "B" Belgyogyaszati osztaly
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Nyiregyhaza, Maďarsko, 4400
- Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
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Kazan, Ruská Federace, 420029
- Republican Clinical Oncology Dispensary
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Perm, Ruská Federace, 614066
- GUZ Perm Regional Oncology Dispensary
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Saint Petersburg, Ruská Federace, 197022
- GUZ City Clinical Oncology Dispensary
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Saint Petersburg, Ruská Federace, 188663
- Leningrad Regional Oncology Dispensary
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Saint Petersburg, Ruská Federace, 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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Alabama
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Mobile, Alabama, Spojené státy, 36604
- USA Mitchell Cancer Institute
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California
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Long Beach, California, Spojené státy, 90813
- Pacific Shores Medical Group
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Los Angeles, California, Spojené státy, 90033
- University of Southern California
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Florida
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Orlando, Florida, Spojené státy, 32804
- Florida Hospital Cancer Institute
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Idaho
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Post Falls, Idaho, Spojené státy, 83854
- Kootenai Cancer Center
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Indiana
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Lafayette, Indiana, Spojené státy, 47905
- The Care Group, LLC. dba Horizon Oncology Center
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Missouri
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Saint Louis, Missouri, Spojené státy, 63110
- Washington University School of Medicine Siteman Cancer Center
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New York
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Lake Success, New York, Spojené státy, 11042
- Arena Oncology Associates, PC
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Ohio
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Dayton, Ohio, Spojené státy, 45420
- Dayton Clinical Oncology Program
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Pennsylvania
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West Reading, Pennsylvania, Spojené státy, 19611
- Berks Hematology Oncology
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Texas
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Richardson, Texas, Spojené státy, 75080
- HOPE Oncology
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San Antonio, Texas, Spojené státy, 78229
- Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development
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Beijing, Čína, 100071
- The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
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Beijing
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Beijing, Beijing, Čína, 100021
- Cancer Hospital, Chinese Academy of Medical Sciences
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Beijing, Beijing, Čína, 100032
- Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
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Jiangsu
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Nanjing, Jiangsu, Čína, 210009
- Jiangsu Cancer Hospital
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Barcelona, Španělsko, 08035
- Hospital Vall d'hebrón
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Madrid, Španělsko, 28040
- Hospital Clinico San Carlos
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Madrid, Španělsko, 28007
- Hospital Gregorio Marañón
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Valencia, Španělsko, 46010
- Hospital Clínico Universitario de Valencia
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Ostatní jména:
Capecitabine orally on days 1-14 of each 21 day cycle
Ostatní jména:
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Experimentální: Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Ostatní jména:
Capecitabine orally on days 1-14 of each 21 day cycle
Ostatní jména:
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Experimentální: Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Ostatní jména:
Capecitabine orally on days 1-14 of each 21 day cycle
Ostatní jména:
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Experimentální: Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Ostatní jména:
Capecitabine orally on days 1-14 of each 21 day cycle
Ostatní jména:
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Experimentální: Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Ostatní jména:
Capecitabine orally on days 1-14 of each 21 day cycle
Ostatní jména:
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Experimentální: 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
Ostatní jména:
Capecitabine orally on days 1-14 of each 21 day cycle
Ostatní jména:
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Experimentální: 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
Ostatní jména:
Capecitabine orally on days 1-14 of each 21 day cycle
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Number of Participants With Dose Limiting Toxicities
Časové okno: 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
Časové okno: 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
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Overall Response Rate
Časové okno: 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
Časové okno: 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
Časové okno: 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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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
9. prosince 2008
Primární dokončení (Aktuální)
1. listopadu 2010
Dokončení studie (Aktuální)
1. června 2018
Termíny zápisu do studia
První předloženo
22. srpna 2008
První předloženo, které splnilo kritéria kontroly kvality
22. srpna 2008
První zveřejněno (Odhad)
26. srpna 2008
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
5. září 2018
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
7. srpna 2018
Naposledy ověřeno
1. srpna 2018
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 3144A1-2206 / B1891017
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