- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01253668
Brivanib Metastatic Renal Cell Carcinoma
18. marts 2021 opdateret af: Abramson Cancer Center of the University of Pennsylvania
Brivanib (BMS-582664, Brivanib Alaninate) in Treatment of Refractory Metastatic Renal Cell Carcinoma - A Phase II Pharmacodynamic and Baseline Biomarker Study
This is a phase II study of an investigational agent, brivanib, in patients with refractory metastatic renal cell carcinoma.
This study will evaluate the safety and effectiveness of brivanib in renal cell carcinoma, and explore the activity of this drug in this population to determine whether imaging and molecular features of the tumors can be used to predict response.
Approximately 30 people with advanced kidney cancer will be enrolled on this study at the University of Pennsylvania.
Studieoversigt
Status
Afsluttet
Betingelser
Detaljeret beskrivelse
The primary objective of this clinical trial is to determine the efficacy of brivanib in the treatment of metastatic renal cell carcinoma in terms of progression-free survival (PFS) in patients who have progressed on treatment with sunitinib, sorafenib, bevacizumab, or pazopanib.
The primary endpoint of the trial will be PFS at 16 weeks.
The secondary objectives are to further examine the safety and tolerability profile of brivanib, to examine the efficacy of brivanib in this population in terms of best overall response, response rate, progression-free survival, and overall survival, to describe baseline and changes in I-cG250 PET/CT in relation to observed therapeutic effects, to describe novel baseline histologic features of these tumors in relation to observed therapeutic effects.
Modalities will include Von Hippel-Lindau gene (VHL) and hypoxia-inducible factor 1 gene (HIF-1) expression assessment and a novel histo-cytometric assessment of the tumor microenvironment in terms of p-STAT3, p-ERK, Ki67, VEGFR2, FGFR1 expression, to describe changes in circulating collagen IV on brivanib in relation to therapeutic effects, to explore the relationship between single nucleotide polymorphisms in angiogenesis-related genes and the activity of brivanib in the treatment of these patients.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
10
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Abramson Cancer Center of the University of Pennsylvania
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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:
- Male and female adults with metastatic renal cell carcinoma
- Patients will have tumors that bear a clear cell component that comprises greater than or equal to 50% of the tumor.
- Disease must be measurable in accord with RECIST 1.1 guidelines.
- Patients who have developed progressive disease or intolerance on treatment with sorafenib, sunitinib, bevacizumab, or pazopanib over a 60 day period who have not discontinued this therapy more than 100 days prior to study enrollment. Progressive disease per RECIST 1.1 guidelines will be preferred
- Therapy with up to three prior systemic regimens will be allowed.
- Patients may have been treated with any of the following: sorafenib, sunitinib, bevacizumab, pazopanib, temsirolimus, everolimus, interferon alpha, interleuken-2.
- Treatment with up to one prior regimen that included cytotoxic chemotherapy will be allowed.
- Patients may have been treated with more than 1 antiangiogenic therapy (e.g., patients may have been treated with both sorafenib and sunitinib or sunitinib and bevacizumab, or sequential combinations that include pazopanib).
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Tumor tissue must be available for correlative studies.
- Patients must consent to allow the acquisition of formalin-fixed paraffin-embedded (FFPE) material (block or unstained slides) by study personnel for performance of correlative tissue studies.
Exclusion Criteria:
- Known brain metastases
- Prior therapy with brivanib, or anti-FGFR (fibroblast growth factor receptor) therapy.
- History of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism.
- Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 4.0 Grade greater than 3 within 30 days prior to study entry.
- Uncontrolled or significant cardiovascular disease.
- QTc greater than 450 msec on two consecutive ECGs (Baseline ECG should be repeated if QTc is found to be greater than 450 msec.).
- Active infection, less than 7 days after completing systemic antibiotic therapy.
- History of non-healing wounds or ulcers or bone fractures within 3 months of fracture.
- Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks prior to study enrollment or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration)within 1 week prior to study enrollment.
- Cytotoxic chemotherapy within 3 weeks, bevacizumab within 2 months, or radiation therapy within 2 weeks, other targeted therapies (e.g., sorafenib, sunitinib, temsirolimus, everolimus)within 2 days.
- Inability to swallow tablets or untreated malabsorption syndrome.
- Pre-existing thyroid abnormality with thyroid function that cannot be controlled with medication.
- History of HIV
- Patients with centrally cavitating lung lesions.
- Patients requiring therapeutic anticoagulation with warfarin at baseline. However, prophylactic therapy with a low molecular weight heparin at baseline is acceptable.
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: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Arm 1
Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.
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Brivanib by mouth daily at a dose of 800mg.
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Andre navne:
Undergo 124I-cG250 PET/CT imaging (correlative studies)
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Correlative studies
correlative studies
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Progression Free Survival (PFS)
Tidsramme: 16 weeks
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All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.
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16 weeks
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Best Overall Response Rated for Each Patients as Assessed by RECIST 1.1 Guidelines
Tidsramme: Every 8 weeks
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The best overall radiographic response to therapy as measured and assessed using RECIST 1.1 guidelines will be captured for each research subject.
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Every 8 weeks
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Overall Survival
Tidsramme: Every 8 weeks
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Will record deaths on study, and, to the extent possible, after the study follow-up period is completed for each patient, will be captured.
Reason for death will be identified and recorded where possible.
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Every 8 weeks
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Change in Total Antibody Binding as Assessed by 124I-cG250 PET/CT Imaging (Correlative Studies)
Tidsramme: At baseline and 8 weeks
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Will determine the baseline and change in total antibody binding in lesions from baseline to the time on treatment that patients are assessed.
The analysis dataset will be quantitated radiotracer uptake data obtained via I-cG250 PET/CT for all evaluable patients who complete the trial.
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At baseline and 8 weeks
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Response Rate for All Patients
Tidsramme: Every 8 weeks
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Response Rate for all patients as assessed by RECIST 1.1 guidelines
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Every 8 weeks
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Molecular Markers
Tidsramme: At baseline
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Molecular markers expressed in patient tumor specimens as assessed by IHC and histocytometry (e.g., VHL, HIF, p-STAT3, p-ERK, and Ki67, VEGFR2, and FGFR1) (correlative studies)
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At baseline
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Changes in Collagen IV Levels
Tidsramme: At baseline and week 3
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Changes in collagen IV levels for each patient (correlative studies)
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At baseline and week 3
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Germline Polymorphisms and Assessment of Relationship to Toxicity and Clinical Outcome
Tidsramme: At baseline and week 3
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Germline polymorphisms and assessment of relationship to toxicity and clinical outcome (correlative studies)
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At baseline and week 3
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Blood Pressure Data
Tidsramme: At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
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Blood pressure data
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At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
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Toxicity as Assessed by NCI CTCAE Version 4.0
Tidsramme: Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter
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Toxicity as assessed by NCI CTCAE version 4.0
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Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
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)
1. november 2011
Primær færdiggørelse (Faktiske)
1. september 2013
Studieafslutning (Faktiske)
1. september 2013
Datoer for studieregistrering
Først indsendt
30. november 2010
Først indsendt, der opfyldte QC-kriterier
2. december 2010
Først opslået (Skøn)
3. december 2010
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
13. april 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
18. marts 2021
Sidst verificeret
1. marts 2021
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Neoplasmer efter histologisk type
- Neoplasmer
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Nyresygdomme
- Urologiske sygdomme
- Adenocarcinom
- Neoplasmer, kirtel og epitel
- Nyre-neoplasmer
- Karcinom, nyrecelle
- Karcinom
- Lægemidlers fysiologiske virkninger
- Immunologiske faktorer
- Antistoffer
- Antistoffer, monoklonale
Andre undersøgelses-id-numre
- UPCC 04810
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 .
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