Try our beta test site

iMATRIXcobi: Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Patients With Previously Treated Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02639546
First received: December 3, 2015
Last updated: November 1, 2016
Last verified: November 2016
  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 and 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.

Condition Intervention Phase
Solid or Brain Tumor With Evidence of RAS/RAF/MEK/ERK Activation
Drug: Cobimetinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 - iMATRIX Cobi

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression Free Survival (PFS) as determined by the Investigator [ Time Frame: Up to 7 years ]
  • Percentage of Participants with dose-limiting toxicities [ Time Frame: Up to Cycle 1 Day 28 ]
  • Maximum Tolerated Dose (MTD) and Maximum Administered Dose (MAD) of cobimetinib [ Time Frame: Up to Cycle 1 Day 28 ]
  • Plasma cobimetinib concentrations [ Time Frame: Cycle 1 Days 1 and 21 (Pre-dose, 2,4,6,and 24 hours post-dose), Cycle 2 Day 1 (Pre-dose) ]
  • Percentage of Participants with Objective Response [ Time Frame: Up to 7 years ]

Secondary Outcome Measures:
  • Duration of Response (DOR) as determined by the Investigator [ Time Frame: Up to 7 years ]
  • Overall Survival [ Time Frame: Up to 7 years ]

Estimated Enrollment: 50
Study Start Date: May 2016
Estimated Study Completion Date: February 2023
Estimated Primary Completion Date: February 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cobimetinib - Dose Escalation Stage
Participants will receive 0.6milligrams 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.
Drug: Cobimetinib
0.6 mg/kg cobimetinib tablets 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 MTD or MAD is determined. During expansion stage participants will be enrolled in disease specific cohorts and treated at or below the MTD or MAD.
Other Name: RO5514041, GDC-0973, XL-518
Experimental: Cobimetinib - Expansion Stage
During expansion stage participants will be enrolled in disease specific cohorts and treated at or below the MTD or MAD determined during dose-escalation.
Drug: Cobimetinib
0.6 mg/kg cobimetinib tablets 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 MTD or MAD is determined. During expansion stage participants will be enrolled in disease specific cohorts and treated at or below the MTD or MAD.
Other Name: RO5514041, GDC-0973, XL-518

  Eligibility

Ages Eligible for Study:   6 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For dose-escalation stage: age at study entry to be greater than (>) 6 years to less than (<) 18 years and weighing >= 20 kilograms
  • For expansion stage: age at study entry to be >6 years to <30 years
  • Histologically or cytologically confirmed tumors 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 DIPG Embryonal rhabdomyosarcoma and other non-rhabdomyosarcoma soft tissue sarcomas Neuroblastoma Melanoma Malignant peripheral nerve sheath tumor Rhabdoid tumors, including 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 International Neuroblastoma Response Criteria, Response Assessment in Neuro-Oncology Criteria, Response Evaluation Criteria in Solid Tumors (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 at least 50 percent
  • Life expectancy of at least 3 months
  • Adequate hematologic, cardiac, and end-organ function
  • Body weight must be greater than or equal to 20 kg

Exclusion Criteria:

  • Pregnant or lactating women
  • Close proximity in time to treatment with high dose chemotherapy, differentiation therapy, immunotherapy, autologous stem cell transplant, radiotherapy, hormonal therapy, hematopoietic growth factor, or investigational therapy according to protocol-defined criteria prior to initiation of study drug
  • Inability to swallow tablets
  • Impaired gastrointestinal absorption
  • History or evidence of retinal pathology according to protocol-defined criteria, including serous retinopathy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02639546

Contacts
Contact: Reference Study ID Number: GO29665 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 37 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02639546     History of Changes
Other Study ID Numbers: GO29665  2014-004685-25 
Study First Received: December 3, 2015
Last Updated: November 1, 2016

ClinicalTrials.gov processed this record on February 24, 2017