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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 febbraio 2020 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

228

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Altri nomi:
  • Tecentriq
Droga: 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.
Sperimentale: 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.
Droga: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Altri nomi:
  • Tecentriq
Droga: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Percentuale di partecipanti con tossicità limitanti la dose (DLT)
Lasso di tempo: Dal giorno 1 al giorno 21
Dal giorno 1 al giorno 21
Number of Participants with Adverse Events (AEs)
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
Maximum-Tolerated Dose (MTD) of RO6958688
Lasso di tempo: 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
Lasso di tempo: Day 1 up to 60 months
Day 1 up to 60 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
PK: Volume of Distribution at Steady State (Vss) of RO6958688
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
PK: Maximum Serum Concentration (Cmax) of RO6958688
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
PK: Clearance (CL) of RO6958688
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
PK: AUC of Atezolizumab
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
PK: Vss of Atezolizumab
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
PK: Cmax of Atezolizumab
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
PK: CL of Atezolizumab
Lasso di tempo: Baseline up to 60 months
Baseline up to 60 months
Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
Lasso di tempo: 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])
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Hoffmann-La Roche

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

7 gennaio 2016

Completamento primario (Effettivo)

13 gennaio 2020

Completamento dello studio (Effettivo)

13 gennaio 2020

Date di iscrizione allo studio

Primo inviato

6 gennaio 2016

Primo inviato che soddisfa i criteri di controllo qualità

6 gennaio 2016

Primo Inserito (Stima)

8 gennaio 2016

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

12 febbraio 2020

Ultimo aggiornamento inviato che soddisfa i criteri QC

10 febbraio 2020

Ultimo verificato

1 febbraio 2020

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • WP29945
  • RG7802 (Altro identificatore: Roche)
  • 2015-003771-30 (Numero EudraCT)

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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Condizioni

Malattie rare

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