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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. Februar 2020 aktualisiert von: 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.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Studientyp

Interventionell

Einschreibung (Tatsächlich)

228

Phase

  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Sequenzielle Zuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Arzneimittel: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Andere Namen:
  • Tecentriq
Arzneimittel: 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.
Experimental: 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.
Arzneimittel: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
Andere Namen:
  • Tecentriq
Arzneimittel: 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.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Zeitfenster
Prozentsatz der Teilnehmer mit dosisbegrenzenden Toxizitäten (DLTs)
Zeitfenster: Tag 1 bis Tag 21
Tag 1 bis Tag 21
Number of Participants with Adverse Events (AEs)
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
Maximum-Tolerated Dose (MTD) of RO6958688
Zeitfenster: 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
Zeitfenster: Day 1 up to 60 months
Day 1 up to 60 months

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
PK: Volume of Distribution at Steady State (Vss) of RO6958688
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
PK: Maximum Serum Concentration (Cmax) of RO6958688
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
PK: Clearance (CL) of RO6958688
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
PK: AUC of Atezolizumab
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
PK: Vss of Atezolizumab
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
PK: Cmax of Atezolizumab
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
PK: CL of Atezolizumab
Zeitfenster: Baseline up to 60 months
Baseline up to 60 months
Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
Zeitfenster: 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])
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Hoffmann-La Roche

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

7. Januar 2016

Primärer Abschluss (Tatsächlich)

13. Januar 2020

Studienabschluss (Tatsächlich)

13. Januar 2020

Studienanmeldedaten

Zuerst eingereicht

6. Januar 2016

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

6. Januar 2016

Zuerst gepostet (Schätzen)

8. Januar 2016

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

12. Februar 2020

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

10. Februar 2020

Zuletzt verifiziert

1. Februar 2020

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • WP29945
  • RG7802 (Andere Kennung: Roche)
  • 2015-003771-30 (EudraCT-Nummer)

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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