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

NCT ID: NCT02639546

Last Updated: 2022-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-20
• Study Completion Date: 2021-07-21

Brief Summary

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.

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I (Tablet) Cobimetinib (0.6 mg/kg)

Dose-Escalation: Participants received 0.6 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Phase I (Tablet) Cobimetinib (0.8 mg/kg)

Dose-Escalation: Participants received 0.8 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Phase I (Tablet) Cobimetinib (1 mg/kg)

Dose-Escalation: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Phase I (Suspension) Cobimetinib (0.6 mg/kg)

Dose-Escalation: Participants received 0.6 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Phase I (Suspension) Cobimetinib (0.8 mg/kg)

Dose-Escalation: Participants received 0.8 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Phase I (Suspension) Cobimetinib (1 mg/kg)

Dose-Escalation: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Phase I (Suspension) Cobimetinib (1.33 mg/kg)

Dose-Escalation: Participants received 1.33 milligrams per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Phase II (Suspension) Cobimetinib (1 mg/kg)

Dose-Expansion: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Interventions

Cobimetinib

Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.

Intervention Type: DRUG

Other Intervention Names

RO5514041, GDC-0973, XL-518

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 criteria for HGG, RANO criteria for LGG, 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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Arkansas Children'S Hospital

Little Rock, Arkansas, United States

Arnold Palmer Hosp-Children

Orlando, Florida, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Hôpital de la Timone, Oncologie Pédiatrique

Marseille, , France

Institut Curie, Oncologie Pédiatrique

Paris, , France

Institut Gustave Roussy; Service Pediatrique

Villejuif, , France

Universitaetsklinikum Muenster

Münster, , Germany

Schneider Children's Medical Center

Petah Tikva, , Israel

Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica

Milan, Lombardy, Italy

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Alderhey Childrens Trust

Liverpool, , United Kingdom

Great Ormond Street Hospital; Dept. Of Pediatric Oncology

London, , United Kingdom

The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit

Newcastle upon Tyne, , United Kingdom

Countries

United States; France; Germany; Israel; Italy; Spain; United Kingdom

References

Trippett T, Toledano H, Campbell Hewson Q, Verschuur A, Langevin AM, Aerts I, Howell L, Gallego S, Rossig C, Smith A, Patel D, Pereira LR, Cheeti S, Musib L, Hutchinson KE, Devlin C, Bernardi R, Geoerger B. Cobimetinib in Pediatric and Young Adult Patients with Relapsed or Refractory Solid Tumors (iMATRIX-cobi): A Multicenter, Phase I/II Study. Target Oncol. 2022 May;17(3):283-293. doi: 10.1007/s11523-022-00888-9. Epub 2022 Jun 17.

Reference Type: DERIVED

PMID: 35715627 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014-004685-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29665

Identifier Type: -

Identifier Source: org_study_id