Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
7. august 2018 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
105
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Queensland
-
South Brisbane, Queensland, Australien, 4101
- Mater Private Centre for HOCA
-
-
Victoria
-
Wodonga, Victoria, Australien, 3690
- Border Medical Oncology
-
-
-
-
RS
-
Porto Alegre, RS, Brasilien, 90035-001
- Associacao Hospitalar Moinhos de Vento Instituto de Edicacao e Pesquisa
-
-
RS - Brazil
-
Ijui, RS - Brazil, Brasilien, 98700-000
- Associacao Hospital de Caridade Ijui
-
-
-
-
-
Kazan, Den Russiske Føderation, 420029
- Republican Clinical Oncology Dispensary
-
Perm, Den Russiske Føderation, 614066
- GUZ Perm Regional Oncology Dispensary
-
Saint Petersburg, Den Russiske Føderation, 197022
- GUZ City Clinical Oncology Dispensary
-
Saint Petersburg, Den Russiske Føderation, 188663
- Leningrad Regional Oncology Dispensary
-
Saint Petersburg, Den Russiske Føderation, 197022
- Saint-Petersburg State Medical University n.a. acad. I.P. Pavlov, Laboratory of Thoracic Oncology of Pulmonology Research Institute
-
-
-
-
Alabama
-
Mobile, Alabama, Forenede Stater, 36604
- USA Mitchell Cancer Institute
-
-
California
-
Long Beach, California, Forenede Stater, 90813
- Pacific Shores Medical Group
-
Los Angeles, California, Forenede Stater, 90033
- University of Southern California
-
-
Florida
-
Orlando, Florida, Forenede Stater, 32804
- Florida Hospital Cancer Institute
-
-
Idaho
-
Post Falls, Idaho, Forenede Stater, 83854
- Kootenai Cancer Center
-
-
Indiana
-
Lafayette, Indiana, Forenede Stater, 47905
- The Care Group, LLC. dba Horizon Oncology Center
-
-
Missouri
-
Saint Louis, Missouri, Forenede Stater, 63110
- Washington University School of Medicine Siteman Cancer Center
-
-
New York
-
Lake Success, New York, Forenede Stater, 11042
- Arena Oncology Associates, PC
-
-
Ohio
-
Dayton, Ohio, Forenede Stater, 45420
- Dayton Clinical Oncology Program
-
-
Pennsylvania
-
West Reading, Pennsylvania, Forenede Stater, 19611
- Berks Hematology Oncology
-
-
Texas
-
Richardson, Texas, Forenede Stater, 75080
- HOPE Oncology
-
San Antonio, Texas, Forenede Stater, 78229
- Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development
-
-
-
-
-
Hong Kong, Hong Kong
- UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
-
-
-
-
-
Beijing, Kina, 100071
- The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
-
-
Beijing
-
Beijing, Beijing, Kina, 100021
- Cancer Hospital, Chinese Academy of Medical Sciences
-
Beijing, Beijing, Kina, 100032
- Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
-
-
Jiangsu
-
Nanjing, Jiangsu, Kina, 210009
- Jiangsu Cancer Hospital
-
-
-
-
-
Seoul, Korea, Republikken, 120-752
- Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine
-
Seoul, Korea, Republikken, 135-710
- Department of Hematology/Oncology, Samsung Medical Center
-
Seoul, Korea, Republikken, 138-736
- Asan Medical Center Department of Medicine Division of Oncology
-
-
-
-
-
Zagreb, Kroatien, 10000
- University Hospital Center Zagreb Department of Oncology
-
-
-
-
-
Singapore, Singapore, 308433
- Johns Hopkins Singapore International Medical Centre
-
-
-
-
-
Barcelona, Spanien, 08035
- Hospital Vall d'hebrón
-
Madrid, Spanien, 28040
- Hospital Clinico San Carlos
-
Madrid, Spanien, 28007
- Hospital Gregorio Marañón
-
Valencia, Spanien, 46010
- Hospital Clínico Universitario de Valencia
-
-
-
-
-
Budapest, Ungarn, 1122
- Országos Onkológiai Intézet "B" Belgyogyaszati osztaly
-
Nyiregyhaza, Ungarn, 4400
- Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
|
Neratinib orally once daily continually
Andre navne:
Capecitabine orally on days 1-14 of each 21 day cycle
Andre navne:
|
|
Eksperimentel: Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
|
Neratinib orally once daily continually
Andre navne:
Capecitabine orally on days 1-14 of each 21 day cycle
Andre navne:
|
|
Eksperimentel: Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
|
Neratinib orally once daily continually
Andre navne:
Capecitabine orally on days 1-14 of each 21 day cycle
Andre navne:
|
|
Eksperimentel: Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
|
Neratinib orally once daily continually
Andre navne:
Capecitabine orally on days 1-14 of each 21 day cycle
Andre navne:
|
|
Eksperimentel: Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
|
Neratinib orally once daily continually
Andre navne:
Capecitabine orally on days 1-14 of each 21 day cycle
Andre navne:
|
|
Eksperimentel: Neratinib and Capecitabine MTD (Dose Group 6)
Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib
|
Neratinib orally once daily continually
Andre navne:
Capecitabine orally on days 1-14 of each 21 day cycle
Andre navne:
|
|
Eksperimentel: Neratinib and Capecitabine MTD (Dose Group 7)
Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib
|
Neratinib orally once daily continually
Andre navne:
Capecitabine orally on days 1-14 of each 21 day cycle
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of Participants With Dose Limiting Toxicities
Tidsramme: From first dose date to day 21
|
Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).
|
From first dose date to day 21
|
|
Maximum Tolerated Dose (MTD) of Neratinib
Tidsramme: From first dose date to day 21.
|
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.
|
From first dose date to day 21.
|
|
Maximum Tolerated Dose (MTD) of Capecitabine
Tidsramme: From first dose date to day 21.
|
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.
|
From first dose date to day 21.
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Overall Response Rate
Tidsramme: From first dose date to progression or last tumor assessment, up to three years.
|
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.
|
From first dose date to progression or last tumor assessment, up to three years.
|
|
Clinical Benefit Rate
Tidsramme: From first dose date to progression or last tumor assessment, up to three years.
|
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.
|
From first dose date to progression or last tumor assessment, up to three years.
|
|
Duration of Response
Tidsramme: From start date of response to first PD/death, up to three years.
|
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.
|
From start date of response to first PD/death, up to three years.
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
9. december 2008
Primær færdiggørelse (Faktiske)
1. november 2010
Studieafslutning (Faktiske)
1. juni 2018
Datoer for studieregistrering
Først indsendt
22. august 2008
Først indsendt, der opfyldte QC-kriterier
22. august 2008
Først opslået (Skøn)
26. august 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
5. september 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
7. august 2018
Sidst verificeret
1. august 2018
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 3144A1-2206 / B1891017
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .