A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors
10 lutego 2020 zaktualizowane przez: Hoffmann-La Roche
An Open-Label, Multicenter, Dose Escalation and Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors
This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab.
Part I of the study is subdivided into parts IA and IB.
Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab.
Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.
Przegląd badań
Typ studiów
Interwencyjne
Zapisy (Rzeczywisty)
228
Faza
- Faza 1
Kontakty i lokalizacje
Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.
Lokalizacje studiów
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København Ø, Dania, 2100
- Rigshospitalet; Onkologisk Klinik
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Lyon, Francja, 69373
- Centre Leon Berard; Departement Oncologie Medicale
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Villejuif, Francja, 94805
- Institut Gustave Roussy
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Barcelona, Hiszpania, 08003
- Hospital del Mar; Servicio de Oncologia
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Barcelona, Hiszpania, 08035
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
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Madrid, Hiszpania, 28041
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
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Madrid, Hiszpania, 28040
- Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
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Madrid, Hiszpania, 28050
- START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
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Navarra
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Pamplona, Navarra, Hiszpania, 31008
- Clinica Universitaria de Navarra; Servicio de Oncologia
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Amsterdam, Holandia, 1066 CX
- Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie
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Ontario
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Toronto, Ontario, Kanada, M5G 1Z5
- Princess Margaret Cancer Center
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California
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Santa Monica, California, Stany Zjednoczone, 90404
- UCLA Cancer Center
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Stanford, California, Stany Zjednoczone, 94305
- Stanford Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, Stany Zjednoczone, 80045
- University of Colorado
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Connecticut
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New Haven, Connecticut, Stany Zjednoczone, 06510
- Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy
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Massachusetts
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Boston, Massachusetts, Stany Zjednoczone, 02215
- Dana Farber Can Ins
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New York
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New York, New York, Stany Zjednoczone, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Stany Zjednoczone, 10032
- Columbia Univ Med Ctr
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North Carolina
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Durham, North Carolina, Stany Zjednoczone, 27710
- Duke Cancer Center
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South Carolina
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Charleston, South Carolina, Stany Zjednoczone, 29425
- Medical University of South Carolina
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Tennessee
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Germantown, Tennessee, Stany Zjednoczone, 38138
- Sarah Cannon Cancer Center
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Texas
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Houston, Texas, Stany Zjednoczone, 77030
- MD Anderson Cancer Center
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Campania
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Napoli, Campania, Włochy, 80131
- IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative
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Toscana
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Siena, Toscana, Włochy, 53100
- Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
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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
- Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
- Radiologically measurable and clinically evaluable disease (as per RECIST v1.1)
- Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate dehydrogenase (LDH) levels </= 2.5 ULN (upper limit of normal)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade </= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy
- Adequate hematological, liver, and renal function
- Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </= 2 years after start of menopause (menopause is defined as amenorrhea for more than 2 years)
- Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol
- Participants with non-colorectal cancer should have confirmed CEA expression in tumor tissue. For colorectal cancer (CRC), the CEA assessment should be performed but the result is not required for participant selection
Exclusion Criteria
- Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to enrollment
- Leptomeningeal disease
- Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 cm unless they are previously irradiated
- Malignancies within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
- Significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results
- Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious cardiac arrhythmia requiring treatment history of myocardial infarction within 6 months of enrollment
- Administration of a live, attenuated vaccine within 28 days before Cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
- Human Inmmunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV)
- Severe infections within 28 days prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or active tuberculosis
- Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- Major surgery or significant traumatic injury less than 28 days prior to Cycle 1 Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
- Known history of autoimmune disease as defined in the protocol
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis (including drug induced) on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Participants with bilateral lung lesions and dyspnea and/or oxygen saturation level (SaO2) less than 92% (at rest, room air and exertion) or participants with lobectomy or pneumonectomy with lung metastases in the remaining lung and either dyspnea or SaO2 less than 92% (at rest, room air and exertion) at baseline
- Pregnant or breast-feeding
- Known hypersensitivity to any of the components of RO6958688 and atezolizumab; hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Investigational therapy (defined as treatment for which there is no regulatory authority approved indication) or last dose of prior immunotherapies within 28 days prior to Cycle 1 Day 1. Participants previously treated with anti-programmed death-ligand 1 (PD-L1), or anti-PD-1 are excluded
- Last dose of any approved anti-cancer therapy within 28 days prior to the first RO6958688 infusion
- Prior systemic corticosteroids greater than 10mg prednisone (or equivalent) within 14 days of Cycle 1 Day 1. Inhaled and/or topical steroids are permitted
- Expected need for regular immunosuppressive therapy
- Radiotherapy within the last 28 days before Cycle 1 Day 1 with the exception of limited-field palliative radiotherapy
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: Randomizowane
- Model interwencyjny: Zadanie sekwencyjne
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: Dose-Escalation (Part IA): RO6958688 + Atezolizumab
Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W).
RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
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Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Inne nazwy:
RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower. |
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Eksperymentalny: Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab
Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first. |
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Inne nazwy:
RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower. |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Ramy czasowe |
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Odsetek uczestników z toksycznością ograniczającą dawkę (DLT)
Ramy czasowe: Dzień 1 do dnia 21
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Dzień 1 do dnia 21
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Number of Participants with Adverse Events (AEs)
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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Maximum-Tolerated Dose (MTD) of RO6958688
Ramy czasowe: Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
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Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
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Recommended Phase II Dose (RP2D) of RO6958688
Ramy czasowe: Day 1 up to 60 months
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Day 1 up to 60 months
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
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Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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PK: Volume of Distribution at Steady State (Vss) of RO6958688
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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PK: Maximum Serum Concentration (Cmax) of RO6958688
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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PK: Clearance (CL) of RO6958688
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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PK: AUC of Atezolizumab
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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PK: Vss of Atezolizumab
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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PK: Cmax of Atezolizumab
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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PK: CL of Atezolizumab
Ramy czasowe: Baseline up to 60 months
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Baseline up to 60 months
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Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
Ramy czasowe: Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
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Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
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Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])
Ramy czasowe: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST
Ramy czasowe: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST
Ramy czasowe: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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Duration of Response (DOR) as Assessed Using RECIST
Ramy czasowe: From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
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Progression-Free Survival (PFS) according to RECIST V1.1
Ramy czasowe: From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
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Overall Survival (OS)
Ramy czasowe: From first study treatment to death from any cause (up to 60 months)
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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From first study treatment to death from any cause (up to 60 months)
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Best Overall Response (BOR)
Ramy czasowe: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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Współpracownicy i badacze
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Publikacje i pomocne linki
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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)
7 stycznia 2016
Zakończenie podstawowe (Rzeczywisty)
13 stycznia 2020
Ukończenie studiów (Rzeczywisty)
13 stycznia 2020
Daty rejestracji na studia
Pierwszy przesłany
6 stycznia 2016
Pierwszy przesłany, który spełnia kryteria kontroli jakości
6 stycznia 2016
Pierwszy wysłany (Oszacować)
8 stycznia 2016
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
12 lutego 2020
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
10 lutego 2020
Ostatnia weryfikacja
1 lutego 2020
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- WP29945
- RG7802 (Inny identyfikator: Roche)
- 2015-003771-30 (Numer EudraCT)
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 .