Ta strona została przetłumaczona automatycznie i dokładność tłumaczenia nie jest gwarantowana. Proszę odnieść się do angielska wersja za tekst źródłowy.

Brivanib Metastatic Renal Cell Carcinoma

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.

Przegląd badań

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

10

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

    • Pennsylvania
      • Philadelphia, Pennsylvania, Stany Zjednoczone, 19104
        • Abramson Cancer Center of the University of Pennsylvania

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:

  • 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.

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: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Arm 1
Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.
Brivanib by mouth daily at a dose of 800mg.
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Inne nazwy:
  • PCR
Undergo 124I-cG250 PET/CT imaging (correlative studies)
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Correlative studies
correlative studies
Inne nazwy:
  • metoda barwienia immunohistochemicznego

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Progression Free Survival (PFS)
Ramy czasowe: 16 weeks
All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.
16 weeks

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Best Overall Response Rated for Each Patients as Assessed by RECIST 1.1 Guidelines
Ramy czasowe: Every 8 weeks
The best overall radiographic response to therapy as measured and assessed using RECIST 1.1 guidelines will be captured for each research subject.
Every 8 weeks
Overall Survival
Ramy czasowe: Every 8 weeks
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.
Every 8 weeks
Change in Total Antibody Binding as Assessed by 124I-cG250 PET/CT Imaging (Correlative Studies)
Ramy czasowe: At baseline and 8 weeks
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.
At baseline and 8 weeks
Response Rate for All Patients
Ramy czasowe: Every 8 weeks
Response Rate for all patients as assessed by RECIST 1.1 guidelines
Every 8 weeks
Molecular Markers
Ramy czasowe: At baseline
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)
At baseline
Changes in Collagen IV Levels
Ramy czasowe: At baseline and week 3
Changes in collagen IV levels for each patient (correlative studies)
At baseline and week 3
Germline Polymorphisms and Assessment of Relationship to Toxicity and Clinical Outcome
Ramy czasowe: At baseline and week 3
Germline polymorphisms and assessment of relationship to toxicity and clinical outcome (correlative studies)
At baseline and week 3
Blood Pressure Data
Ramy czasowe: At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
Blood pressure data
At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
Toxicity as Assessed by NCI CTCAE Version 4.0
Ramy czasowe: Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter
Toxicity as assessed by NCI CTCAE version 4.0
Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

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)

1 listopada 2011

Zakończenie podstawowe (Rzeczywisty)

1 września 2013

Ukończenie studiów (Rzeczywisty)

1 września 2013

Daty rejestracji na studia

Pierwszy przesłany

30 listopada 2010

Pierwszy przesłany, który spełnia kryteria kontroli jakości

2 grudnia 2010

Pierwszy wysłany (Oszacować)

3 grudnia 2010

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

13 kwietnia 2021

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

18 marca 2021

Ostatnia weryfikacja

1 marca 2021

Więcej informacji

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 .

Badania kliniczne na Rak nerkowokomórkowy

Badania kliniczne na Brivanib alaninate

3
Subskrybuj