Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
7 agosto 2018 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
105
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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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, Brasile, 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, Brasile, 98700-000
- Associacao Hospital de Caridade Ijui
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Beijing, Cina, 100071
- The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
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Beijing
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Beijing, Beijing, Cina, 100021
- Cancer Hospital, Chinese Academy of Medical Sciences
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Beijing, Beijing, Cina, 100032
- Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
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Jiangsu
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Nanjing, Jiangsu, Cina, 210009
- Jiangsu Cancer Hospital
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Seoul, Corea, Repubblica di, 120-752
- Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine
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Seoul, Corea, Repubblica di, 135-710
- Department of Hematology/Oncology, Samsung Medical Center
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Seoul, Corea, Repubblica di, 138-736
- Asan Medical Center Department of Medicine Division of Oncology
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Zagreb, Croazia, 10000
- University Hospital Center Zagreb Department of Oncology
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Kazan, Federazione Russa, 420029
- Republican Clinical Oncology Dispensary
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Perm, Federazione Russa, 614066
- GUZ Perm Regional Oncology Dispensary
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Saint Petersburg, Federazione Russa, 197022
- GUZ City Clinical Oncology Dispensary
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Saint Petersburg, Federazione Russa, 188663
- Leningrad Regional Oncology Dispensary
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Saint Petersburg, Federazione Russa, 197022
- Saint-Petersburg State Medical University n.a. acad. I.P. Pavlov, Laboratory of Thoracic Oncology of Pulmonology Research Institute
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Hong Kong, Hong Kong
- UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
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Singapore, Singapore, 308433
- Johns Hopkins Singapore International Medical Centre
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Barcelona, Spagna, 08035
- Hospital Vall d'hebrón
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Madrid, Spagna, 28040
- Hospital Clinico San Carlos
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Madrid, Spagna, 28007
- Hospital Gregorio Marañón
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Valencia, Spagna, 46010
- Hospital Clínico Universitario de Valencia
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Alabama
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Mobile, Alabama, Stati Uniti, 36604
- USA Mitchell Cancer Institute
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California
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Long Beach, California, Stati Uniti, 90813
- Pacific Shores Medical Group
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Los Angeles, California, Stati Uniti, 90033
- University of Southern California
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Florida
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Orlando, Florida, Stati Uniti, 32804
- Florida Hospital Cancer Institute
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Idaho
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Post Falls, Idaho, Stati Uniti, 83854
- Kootenai Cancer Center
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Indiana
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Lafayette, Indiana, Stati Uniti, 47905
- The Care Group, LLC. dba Horizon Oncology Center
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Missouri
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Saint Louis, Missouri, Stati Uniti, 63110
- Washington University School of Medicine Siteman Cancer Center
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New York
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Lake Success, New York, Stati Uniti, 11042
- Arena Oncology Associates, PC
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Ohio
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Dayton, Ohio, Stati Uniti, 45420
- Dayton Clinical Oncology Program
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Pennsylvania
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West Reading, Pennsylvania, Stati Uniti, 19611
- Berks Hematology Oncology
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Texas
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Richardson, Texas, Stati Uniti, 75080
- HOPE Oncology
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San Antonio, Texas, Stati Uniti, 78229
- Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development
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Budapest, Ungheria, 1122
- Országos Onkológiai Intézet "B" Belgyogyaszati osztaly
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Nyiregyhaza, Ungheria, 4400
- Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Altri nomi:
Capecitabine orally on days 1-14 of each 21 day cycle
Altri nomi:
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Sperimentale: Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
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Neratinib orally once daily continually
Altri nomi:
Capecitabine orally on days 1-14 of each 21 day cycle
Altri nomi:
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Sperimentale: Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Altri nomi:
Capecitabine orally on days 1-14 of each 21 day cycle
Altri nomi:
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Sperimentale: Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Altri nomi:
Capecitabine orally on days 1-14 of each 21 day cycle
Altri nomi:
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Sperimentale: Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
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Neratinib orally once daily continually
Altri nomi:
Capecitabine orally on days 1-14 of each 21 day cycle
Altri nomi:
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Sperimentale: 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
Altri nomi:
Capecitabine orally on days 1-14 of each 21 day cycle
Altri nomi:
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Sperimentale: 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
Altri nomi:
Capecitabine orally on days 1-14 of each 21 day cycle
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Number of Participants With Dose Limiting Toxicities
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Overall Response Rate
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
9 dicembre 2008
Completamento primario (Effettivo)
1 novembre 2010
Completamento dello studio (Effettivo)
1 giugno 2018
Date di iscrizione allo studio
Primo inviato
22 agosto 2008
Primo inviato che soddisfa i criteri di controllo qualità
22 agosto 2008
Primo Inserito (Stima)
26 agosto 2008
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
5 settembre 2018
Ultimo aggiornamento inviato che soddisfa i criteri QC
7 agosto 2018
Ultimo verificato
1 agosto 2018
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 3144A1-2206 / B1891017
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Sì
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .