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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. února 2020 aktualizováno: 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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

228

Fáze

  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Dánsko
      • København Ø, Dánsko, 2100
        • Rigshospitalet; Onkologisk Klinik
  • Francie
      • Lyon, Francie, 69373
        • Centre Leon Berard; Departement Oncologie Medicale
      • Villejuif, Francie, 94805
        • Institut Gustave Roussy
  • Holandsko
      • Amsterdam, Holandsko, 1066 CX
        • Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie
  • Itálie
    • Campania
      • Napoli, Campania, Itálie, 80131
        • IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative
    • Toscana
      • Siena, Toscana, Itálie, 53100
        • Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
  • Kanada
    • Ontario
      • Toronto, Ontario, Kanada, M5G 1Z5
        • Princess Margaret Cancer Center
  • Spojené státy
    • California
      • Santa Monica, California, Spojené státy, 90404
        • UCLA Cancer Center
      • Stanford, California, Spojené státy, 94305
        • Stanford Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, Spojené státy, 80045
        • University of Colorado
    • Connecticut
      • New Haven, Connecticut, Spojené státy, 06510
        • Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy
    • Massachusetts
      • Boston, Massachusetts, Spojené státy, 02215
        • Dana Farber Can Ins
    • New York
      • New York, New York, Spojené státy, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, Spojené státy, 10032
        • Columbia Univ Med Ctr
    • North Carolina
      • Durham, North Carolina, Spojené státy, 27710
        • Duke Cancer Center
    • South Carolina
      • Charleston, South Carolina, Spojené státy, 29425
        • Medical University of South Carolina
    • Tennessee
      • Germantown, Tennessee, Spojené státy, 38138
        • Sarah Cannon Cancer Center
    • Texas
      • Houston, Texas, Spojené státy, 77030
        • MD Anderson Cancer Center
  • Španělsko
      • Barcelona, Španělsko, 08003
        • Hospital del Mar; Servicio de Oncologia
      • Barcelona, Španělsko, 08035
        • Hospital Univ Vall d'Hebron; Servicio de Oncologia
      • Madrid, Španělsko, 28041
        • Hospital Universitario 12 de Octubre; Servicio de Oncologia
      • Madrid, Španělsko, 28040
        • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
      • Madrid, Španělsko, 28050
        • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
    • Navarra
      • Pamplona, Navarra, Španělsko, 31008
        • Clinica Universitaria de Navarra; Servicio de Oncologia

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Sekvenční přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Ostatní jména:
  • Tecentriq
Lék: RO6958688

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.
Experimentální: 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.
Lék: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Ostatní jména:
  • Tecentriq
Lék: RO6958688

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 je měření studie?

Primární výstupní opatření

Měření výsledku
Časové okno
Procento účastníků s toxicitou omezující dávku (DLT)
Časové okno: Den 1 až den 21
Den 1 až den 21
Number of Participants with Adverse Events (AEs)
Časové okno: Baseline up to 60 months
Baseline up to 60 months
Maximum-Tolerated Dose (MTD) of RO6958688
Časové okno: Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
Recommended Phase II Dose (RP2D) of RO6958688
Časové okno: Day 1 up to 60 months
Day 1 up to 60 months

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
Časové okno: Baseline up to 60 months
Baseline up to 60 months
PK: Volume of Distribution at Steady State (Vss) of RO6958688
Časové okno: Baseline up to 60 months
Baseline up to 60 months
PK: Maximum Serum Concentration (Cmax) of RO6958688
Časové okno: Baseline up to 60 months
Baseline up to 60 months
PK: Clearance (CL) of RO6958688
Časové okno: Baseline up to 60 months
Baseline up to 60 months
PK: AUC of Atezolizumab
Časové okno: Baseline up to 60 months
Baseline up to 60 months
PK: Vss of Atezolizumab
Časové okno: Baseline up to 60 months
Baseline up to 60 months
PK: Cmax of Atezolizumab
Časové okno: Baseline up to 60 months
Baseline up to 60 months
PK: CL of Atezolizumab
Časové okno: Baseline up to 60 months
Baseline up to 60 months
Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
Časové okno: 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)
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)
Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])
Časové okno: Baseline up to 60 months
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.
Baseline up to 60 months
Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST
Časové okno: Baseline up to 60 months
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.
Baseline up to 60 months
Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST
Časové okno: Baseline up to 60 months
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.
Baseline up to 60 months
Duration of Response (DOR) as Assessed Using RECIST
Časové okno: From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
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.
From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
Progression-Free Survival (PFS) according to RECIST V1.1
Časové okno: From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
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.
From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
Overall Survival (OS)
Časové okno: From first study treatment to death from any cause (up to 60 months)
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.
From first study treatment to death from any cause (up to 60 months)
Best Overall Response (BOR)
Časové okno: Baseline up to 60 months
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.
Baseline up to 60 months

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Hoffmann-La Roche

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

7. ledna 2016

Primární dokončení (Aktuální)

13. ledna 2020

Dokončení studie (Aktuální)

13. ledna 2020

Termíny zápisu do studia

První předloženo

6. ledna 2016

První předloženo, které splnilo kritéria kontroly kvality

6. ledna 2016

První zveřejněno (Odhad)

8. ledna 2016

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

12. února 2020

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

10. února 2020

Naposledy ověřeno

1. února 2020

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • WP29945
  • RG7802 (Jiný identifikátor: Roche)
  • 2015-003771-30 (Číslo EudraCT)

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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