Clinical Trials /

Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors

NCT02639546

Description:

This open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of cobimetinib in pediatric and young adult participants with solid tumors with known or potential kinase pathway activation for which standard therapy has proven to be ineffective or intolerable or for which no curative standard-of-care treatment options exist. The study will be conducted in two stages: a dose-escalation stage and an expansion stage at the recommended dose.

Related Conditions:
  • Glioma
  • Malignant Peripheral Nerve Sheath Tumor
  • Neuroblastoma
  • Rhabdoid Tumor
  • Rhabdomyosarcoma
  • Schwannoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors
  • Official Title: A Phase I/II, Multicenter, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Cobimetinib In Pediatric and Young Adult Patients With Previously Treated Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GO29665
  • SECONDARY ID: 2014-004685-25
  • NCT ID: NCT02639546

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
CobimetinibRO5514041, GDC-0973, XL-518Cobimetinib - Dose-Escalation Stage

Purpose

This open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of cobimetinib in pediatric and young adult participants with solid tumors with known or potential kinase pathway activation for which standard therapy has proven to be ineffective or intolerable or for which no curative standard-of-care treatment options exist. The study will be conducted in two stages: a dose-escalation stage and an expansion stage at the recommended dose.

Trial Arms

NameTypeDescriptionInterventions
Cobimetinib - Dose-Escalation StageExperimentalParticipants will receive 0.6 milligrams per kilogram (mg/kg) cobimetinib by mouth once daily on Days 1 to 21 of each 28-day treatment cycle. The dose will be increased by up to approximately 33% of the preceding dose level for each successive cohort until maximum tolerated dose (MTD) or maximum administered dose (MAD) is determined. Once MTD or MAD has been identified in tablets, enrollment of participants using suspension will commence at a minimum of one dose level below MTD or MAD of the tablets.
  • Cobimetinib
Cobimetinib - Expansion StageExperimentalDuring the expansion stage, participants will be enrolled in disease-specific cohorts and treated at or below the MTD or MAD determined during the dose-escalation stage for pediatric participants and at the recommended adult dose for participants greater than or equal to (>=) 18 years.
  • Cobimetinib

Eligibility Criteria

        Inclusion Criteria:

          -  For dose-escalation stage (tablets): age at study entry >= 6 years to < 18 years

          -  For dose-escalation stage (suspension): age at study entry >= 6 months to < 18 years.
             Participants <1 year of age will not be enrolled until >= 6 participants >= 1 year to
             < 18 years of age have received at least one cycle of therapy with suspension and
             until safety and pharmacokinetic assessment of these participants have been conducted.

          -  For expansion stage: age at study entry to be >= 6 months (>=6 years if suspension is
             not available) to < 30 years. Participants >= 6 months to < 1 year of age may not be
             enrolled until >= 6 participants >= 1 year to < 18 years of age have received at least
             one cycle of therapy with suspension in the dose-escalation phase and until safety and
             pharmacokinetic assessment of these participants have been conducted.

          -  Tumor for which prior treatment has proven to be ineffective or intolerable or for
             which no standard therapy exists

          -  Tumor with known or expected RAS/RAF/MEK/ERK pathway involvement. Diagnosis must be
             one of the following tumor types:

        Central nervous system gliomas, including high- and low-grade gliomas, and diffuse
        intrinsic pontine glioma (DIPG) Embryonal rhabdomyosarcoma and other non-rhabdomyosarcoma
        soft tissue sarcomas Neuroblastoma Melanoma Malignant peripheral nerve sheath tumor
        Rhabdoid tumors, including atypical teratoid/rhabdoid tumor (ATRT) NF1-associated tumor
        (including plexiform neurofibroma), schwannoma, or RASopathy-associated tumor that in the
        judgment of the investigator is life threatening, results in severe symptoms (including
        severe pain), or is in close proximity to vital structures

          -  Measurable disease as defined by mINRC, RANO, RECIST v1.1, or evaluable by nuclear
             medicine techniques, immunocytochemistry, tumor markers, or other reliable measures

          -  Availability of tumor tissue at study enrollment

          -  Lansky performance status or Karnofsky performance status of >= 50 percent

          -  Life expectancy >= 3 months

          -  Adequate hematologic, cardiac, and end-organ function

          -  Body weight must be >= 20 kilograms (kg) if suspension is not available

        Exclusion Criteria:

          -  Pregnant or lactating women

          -  Close proximity in time to treatment with high-dose chemotherapy, stem-cell rescue,
             differentiation therapy, immunotherapy, thoracic or mediastinal radiotherapy, hormonal
             therapy, biologic therapy, herbal cancer therapy, hematopoietic growth factor,
             investigational therapy, or St. John's wort according to protocol-defined criteria
             prior to initiation of study drug

          -  Inability to swallow oral medications

          -  Impaired gastrointestinal absorption

          -  History or evidence of retinal pathology according to protocol-defined criteria,
             including serous retinopathy

          -  History of Grade >= 2 central nervous system (CNS) hemorrhage

          -  History of CNS hemorrhage within 28 days of study entry. This criterion may be waived
             at the investigator's request if the CNS hemorrhage was asymptomatic, with approval of
             the Medical Monitor

          -  Known active infection (excluding fungal infection of the nail beds) within 28 days
             prior to initiation of study drug that has not completely resolved

          -  Major surgical procedure or significant traumatic injury within 4 weeks prior to
             initiation of study drug, or anticipation of need for major surgical procedure during
             the course of the study

          -  Prior allogenic bone marrow transplantation or prior solid organ transplantation
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame:Cycle 1 Day 1 up to Cycle 1 Day 28 (cycle length=28 days)
Safety Issue:
Description:Tumor assessment will be performed using modified International Neuroblastoma Response Criteria (mINRC) for participants with neuroblastoma, Response Assessment in Neuro-Oncology (RANO) criteria for participants with high-grade glioma (HGG), and Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) for participants with other tumors.

Secondary Outcome Measures

Measure:Duration of Response (DOR) as Determined by the Investigator
Time Frame:From first occurrence of objective response to disease progression or death due to any cause, whichever occurs first (up to 6.75 years)
Safety Issue:
Description:Tumor assessment will be performed using mINRC for participants with neuroblastoma, RANO criteria for participants with HGG, and RECIST v1.1 for participants with other tumors.
Measure:Overall Survival
Time Frame:Baseline until death due to any cause (up to 6.75 years)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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