- ICH GCP
- Rejestr badań klinicznych w USA
- Badanie kliniczne NCT01959490
Trastuzumab and Pertuzumab or Bevacizumab With Combination Chemotherapy in Treating Patients With Stage II-III Breast Cancer
Next Generation Sequencing to Evaluate Breast Cancer Subtypes and Genomic Predictors of Response to Therapy in the Preoperative Setting for Stage II-III Breast Cancer
Przegląd badań
Status
Warunki
Szczegółowy opis
PRIMARY OBJECTIVES:
I. To determine if genomically derived 'molecular subtypes' predict pathological complete response to combination chemotherapy and targeted therapy for HER2 early stage breast cancer.
SECONDARY OBJECTIVES:
I. To explore the ability of trastuzumab or pertuzumab response signatures to predict pCR in HER2 positive tumors treated with brief exposure to trastuzumab or pertuzumab followed by combination chemotherapy.
II. To explore the value of immune signatures as well as AKT and IGF signatures to predict pCR in HER2 tumors treated with brief exposure to trastuzumab and pertuzumab.
III. To explore if comprehensive annotation of genomic alterations (mutations, copy number alternations, gene fusions, non-coding RNA and splice variants) can further sub-stratify subtype-based classifiers for prediction of response to targeted therapy in early stage breast cancer IV. To explore if circulating RNA expression levels are associated with treatment response V. To explore changes in cardiac function and identify early cardiac injury using strain echocardiograms and cardiac biomarkers during treatment VI. To explore immunohistochemistry-based markers of response to treatment
Objectives for Imaging Sub-Study: Secondary Objectives I. Evaluate the visualization of primary breast tumors using analog and digital positron emission tomography (PET) with FDG and FLT. II. Evaluate the quantification of FDG-uptake in primary breast tumors using analog and digital PET with FDG and FLT. III. Compare the levels and changes in metabolic tumor activity from analog and digital FDG-PET/CT or FLT-PET/CT with clinical follow up and other procures include into CASE 14112 (such as DCE-MRI, genetic testing, etc.)
OUTLINE: Patients are assigned to 1 of 2 treatment cohorts based on HER2 status.
COHORT I (HER2 positive): Patients receive trastuzumab intravenously (IV) over 30-60 minutes, and pertuzumab IV over 30-60 minutes, docetaxel IV, and carboplatin IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. As part of standard of care, each patient will receive three MRIs pre-treatment, before biopsy is taken, and before surgery. Ten additional patients will be added to cohort 1 to take part in the imaging sub-study. These ten patients will follow the same procedure as the other participants in cohort I but will have a PET/CT in place of the DCE-MRI
COHORT II (HER2 negative): Patients receive bevacizumab IV over 30-60 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11; doxorubicin IV and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 3, 5, and 7; and paclitaxel IV over 3 hours on day 1 of weeks 9, 11, 13, and 15. Prior to receiving paclitaxel patients will receive the anti-nausea medication
After completion of study treatment, patients are followed up for 30 days.
Typ studiów
Zapisy (Rzeczywisty)
Faza
- Faza 2
Kontakty i lokalizacje
Lokalizacje studiów
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Ohio
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Cleveland, Ohio, Stany Zjednoczone, 44106-5065
- University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
Inclusion Criteria:
Histologically confirmed adenocarcinoma of the breast, with sufficient tissue available for estrogen receptor (ER), progesterone receptor (PR), and HER 2 testing
- HER2 must be positive by IHC or ISH testing by laboratory standard.
- Needle biopsy or incisional biopsy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- Resectable disease-clinical stage I (T/0/N0miT1N0-N0mi), IIA-IIIA (T2 N0/T3N0 or T1-3 N1-N2a) or unresectable disease - clinical stage IIIB/IIIC (T4 or T1-3 N2b-3); no evidence of metastatic disease
- No prior chemotherapy, hormonal therapy, or radiation therapy for this cancer
- Absolute neutrophil count (ANC) ≥1000/ul
- Platelet count ≥ 100,000/ul
- Hemoglobin ≥ 9 g/dl
- Serum creatinine ≤ 1.5 mg/dl or measured creatinine clearance of > 30 ml/min
- Total bilirubin ≤ upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN
- Patients with multiple foci of invasive cancer in the same breast are eligible if any single lesion meets the above size criteria and all sampled lesions are histologically similar (whether radiographically detected lesions separate from the target lesion are sampled for histologic evaluation is left to the discretion of the treating physicians); the presence of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) in either breast will not render a patient ineligible; patients with a small focus of invasive cancer detected the contralateral breast (clinical T1N0) are eligible, however only the histologic response in the breast containing the target lesions will be considered in determining the patient's pathologic response
- Measurable disease in the breast or axilla that measures at least 1 cm by either clinical or radiographic measurement
Exclusion Criteria:
- Excisional biopsy
- Pregnant and lactating women are not eligible; all participants of reproductive age must have a negative serum pregnancy test at baseline and agree to use an effective barrier method of contraception during the entire period of treatment on the study
- Patients with New York Heart Association (NYHA) grade 2 or higher congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, or arterial thrombotic event with the past 12 months, uncontrolled hypertension (systolic blood pressure > 150 and/or diastolic blood pressure > 100 on antihypertensive medications; patients not on medication for high blood pressure who are found to have systolic blood pressure [SBP] > 150 and/or diastolic blood pressure [DBP] > 100 should have 3 documented episodes of elevated blood pressure before being considered 'uncontrolled', if they have 3 documented episodes of elevated blood pressure, then can be started on antihypertensive medications; patients currently on antihypertensive medications with elevated blood pressures as defined above may have their medications adjusted; if patients have persistent [3 episodes] of high blood pressure despite medication adjustment they will be considered ineligible for study participation; each measured episode should be 24 hours apart), prior history of hypertensive crisis or hypertensive encephalopathy, uncontrolled or clinically significant arrhythmia, grade II or greater peripheral vascular disease or prior history of stroke or transient ischemic attack (TIA); patient must have a pretreatment multi gated acquisition scan (MUGA) scan or echocardiogram with left ventricular ejection fraction (LVEF) above lower limit of normal
- No non-breast malignancy within the past 5 years other than treated squamous or basal cell carcinoma of the skin or CIS of the cervix
- Patients known to be human immunodeficiency virus (HIV) positive are not eligible for the study given their potentially compromised immune systems and increased risk of treatment-related toxicity
- Advanced (T1N1-4/T2-3 N any) invasive cancer in the contralateral breast
- Any known history of cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage
- Patients must not have a non-healing wound or fracture
- Patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months
- Patients must not have a bleeding diathesis, hereditary of acquired bleeding disorder or coagulopathy
- Patients on therapeutic doses of Coumadin or Lovenox are ineligible to participate in study
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study; core biopsy or other minor surgical procedure, for example placement of a vascular access device, are excluded from this requirement
- No known hypersensitivity to any component of bevacizumab
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Podstawowa nauka
- Przydział: Nielosowe
- Model interwencyjny: Przydział równoległy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: Cohort 1P (HER2 positive)
Patients receive a run-in Pertuzumab treatment of 840 mg IV over 60 minutes on day -14 followed by Trastuzumab IV over 30-60 minutes and Pertuzumab IV over 30-60 minutes, docetaxel IV, and carboplatin IV on day 1.
Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
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Biorąc pod uwagę IV
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
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Eksperymentalny: Cohort 1T (HER2 positive)
Patients receive a run-in Trastuzumab treatment of 8 mg/kg IV over 90 minutes on day -14 followed by Trastuzumab IV over 30-60 minutes and Pertuzumab IV over 30-60 minutes, Docetaxel IV, and Carboplatin IV on day 1.
Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
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Biorąc pod uwagę IV
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
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Eksperymentalny: Cohort II (HER2 negative)
Patients receive Bevacizumab IV over 30-60 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11; Doxorubicin IV and Cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 3, 5, and 7; and Paclitaxel IV over 3 hours on day 1 of weeks 9, 11, 13, and 15.
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Biorąc pod uwagę IV
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
Inne nazwy:
Biorąc pod uwagę IV
Inne nazwy:
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
---|---|---|
Number of Patients With a Pathological Complete Response (pCR) Who Received Targeted Therapy With Trastuzumab and Pertuzumab or Bevacizumab Predicted by Genomically-derived Molecular Subtypes.
Ramy czasowe: Up to 30 days after last cycle of treatment
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Number of patients with a pathological complete response (pCR) who received targeted therapy with trastuzumab and pertuzumab or bevacizumab predicted by genomically-derived molecular subtypes (HER2 positive or HER2 negative.
pCR is defined as absence of invasive cancer in breast or lymph nodes after neoadjuvant chemotherapy.
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Up to 30 days after last cycle of treatment
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
---|---|---|
The Number of HER2 Positive Patients With a Pathological Complete Response (pCR) Predicted by a Trastuzumab and Pertuzumab Response Signature
Ramy czasowe: Up to 30 days after last cycle of treatment
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Up to 30 days after last cycle of treatment
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The Number of HER2 Negative Patients With a pCR Predicted by the TGF-B Response Signature
Ramy czasowe: Up to 30 days after last cycle of treatment
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Up to 30 days after last cycle of treatment
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The Number of HER2 Positive Patients With a pCR Predicted by the AKT Signature and IGF Signature.
Ramy czasowe: Up to 30 days after last cycle of treatment
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Up to 30 days after last cycle of treatment
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The Number of Patients With a pCR Predicated by Copy Number Alterations.
Ramy czasowe: Up to 30 days after last cycle of treatment
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Up to 30 days after last cycle of treatment
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The Number of Patients With a pCR Predicted by Changes in Texture on Breast DCE-MRI After a Two-week "run-in" Treatment With Trastuzumab, Pertuzumab, or Bevacizumab
Ramy czasowe: At 2 weeks after start of run-in period
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Determine if changes in regularity and entropy range predict pCR and in an exploratory fashion determine if specific texture features exist in each molecular subtype that predict pCR.
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At 2 weeks after start of run-in period
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Inne miary wyników
Miara wyniku |
Opis środka |
Ramy czasowe |
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Descriptive Statistics of PET/CT Scan
Ramy czasowe: Up to 30 days after last cycle of treatment
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Qualitative and quantitative image analysis will be performed and descriptively summarized.
For the 10 patients in the PET/CT sub-study of cohort 1.
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Up to 30 days after last cycle of treatment
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Współpracownicy i badacze
Sponsor
Współpracownicy
Śledczy
- Główny śledczy: Paula Silverman, MD, Case Comprehensive Cancer Center
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Rzeczywisty)
Ukończenie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Oszacować)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
- Choroby skórne
- Nowotwory
- Nowotwory według lokalizacji
- Choroby piersi
- Nowotwory piersi
- Fizjologiczne skutki leków
- Molekularne mechanizmy działania farmakologicznego
- Inhibitory enzymów
- Środki przeciwreumatyczne
- Środki przeciwnowotworowe
- Środki immunosupresyjne
- Czynniki immunologiczne
- Modulatory tubuliny
- Środki antymitotyczne
- Modulatory mitozy
- Środki przeciwnowotworowe, alkilujące
- Środki alkilujące
- Agoniści mieloablacyjni
- Środki przeciwnowotworowe, Fitogenne
- Inhibitory topoizomerazy II
- Inhibitory topoizomerazy
- Środki przeciwnowotworowe, immunologiczne
- Inhibitory angiogenezy
- Środki modulujące angiogenezę
- Substancje wzrostowe
- Inhibitory wzrostu
- Antybiotyki, Przeciwnowotworowe
- Docetaksel
- Cyklofosfamid
- Karboplatyna
- Paklitaksel
- Trastuzumab
- Bewacyzumab
- Doksorubicyna
- Liposomalna doksorubicyna
- Pertuzumab
Inne numery identyfikacyjne badania
- CASE14112
- P30CA043703 (Grant/umowa NIH USA)
- NCI-2013-01422 (Identyfikator rejestru: CTRP (Clinical Trial Reporting Program))
- CASE 14112 (Inny identyfikator: Case Comprehensive Cancer Center)
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