Solid TumorsPhase 1/2iMATRIXcobiNCT02639546
Safety and Pharmacokinetics of Cobimetinib in Pediatric and Young Adult Participants With Previously Treated Solid Tumors
A Phase 1/2 study testing Cobimetinib in people with Solid Tumors, run by Hoffmann-La Roche at 17 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 months to 30 years
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Cobimetinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 17 sitesin 7 countries
- Study dates
- 20 May 2016to 21 Jul 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
United States5 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Arkansas Children'S Hospital
Little Rock, Arkansas, 72202
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Arnold Palmer Hosp-Children
Orlando, Florida, 32806
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
France3 sites
Hôpital de la Timone, Oncologie Pédiatrique
Marseille, 13385
Institut Curie, Oncologie Pédiatrique
Paris, 75231
Institut Gustave Roussy; Service Pediatrique
Villejuif, 94805
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Infantil Universitario Nino Jesus
Madrid, 28009
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
United Kingdom3 sites
Alderhey Childrens Trust
Liverpool, L12 2AP
Great Ormond Street Hospital; Dept. Of Pediatric Oncology
London, WC1N 3JH
The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit
Newcastle upon Tyne, NE1 4LP
Italy1 site
Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica
Milan, Lombardy, 20133
About this study
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
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
- Being tested
- Cobimetinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobimetinibDrug
Also called RO5514041, GDC-0973, XL-518
Cobimetinib tablet or suspension will be administered as per the schedule described in arm description.
| Study group | Role | What they receive |
|---|---|---|
| Phase I (Tablet) Cobimetinib (0.6 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
| Phase I (Tablet) Cobimetinib (0.8 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
| Phase I (Tablet) Cobimetinib (1 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
| Phase I (Suspension) Cobimetinib (0.6 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
| Phase I (Suspension) Cobimetinib (0.8 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
| Phase I (Suspension) Cobimetinib (1 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
| Phase I (Suspension) Cobimetinib (1.33 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
| Phase II (Suspension) Cobimetinib (1 mg/kg) | Experimental | 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. Receives: Drug: Cobimetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Dose-Limiting Toxicities (DLTs) were defined as cobimetinib-related adverse events occurring within the first 28 days of each administration of cobimetinib.
Measured: Baseline up until 30 days after the last dose of study drug (up to 5 years, 2 months)
Percentage of Participants With Adverse Events (AEs), Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs.
Measured: Baseline up until 30 days after the last dose of study drug (up to 5 years, 2 months)
Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Cobimetinib
A prior dose level was defined as an MTD/MAD if at a certain dose level, there were greater than or equal to (>=) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs).
Measured: Cycle 1 Day 1 up to Cycle 1 Day 28 (cycle length=28 days)
Percentage of Participants With Objective Response (Complete Response (CR) or Partial Response (PR)) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) for Participants With Neuroblastoma (Phase I)
Tumor assessment was performed using mINRC for Participants with Neuroblastoma.
Measured: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RANO Criteria for Participants With High-Grade Glioma (HGG) (Phase I) and RECIST v1.1 for Participants With Low-Grade Glioma (LGG) (Phase I and II)
Tumor assessment was performed using Response Assessment in Neuro-Oncology (RANO) criteria for participants with HGG and Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.
Measured: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RECIST v1.1 Criteria for Participants With All Other Tumours (Phase I)
Tumor assessment was performed using RECIST v1.1 for Participants with All Other Tumours.
Measured: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II)
Tumor assessment will be performed using RANO criteria for LGG.
Measured: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Progression-Free Survival (PFS) as Determined by the Investigator Using mINRC for Participants With Neuroblastoma (Phase I)
Tumor assessment was performed using mINRC for Participants with Neuroblastoma.
Measured: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
PFS as Determined by the Investigator Using RANO Criteria for Participants With HGG (Phase I) and RECIST v1.1 for Partcipants With LGG (Phase I and II)
Tumor assessment was performed using RANO for participants with HGG and RECIST v1.1 for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.
Measured: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
PFS as Determined by the Investigator Using RECIST v1.1 Criteria for Participants With All Other Tumours (Phase I)
Tumor assessment was performed using RECIST v1.1 for Participants with All Other Tumours.
Measured: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
PFS as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II)
Tumor assessment was performed using RANO criteria for Participants with LGG.
Measured: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Secondary outcomes (10)
Recommended Phase II Dose (RP2D) of Cobimetinib
A prior dose level was defined as an RP2D if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs).
Measured: Cycle 1 Day 1 up to Cycle 1 Day 28 (cycle length=28 days)
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 for Participants With LGG (Phase I and II)
Tumor assessment was performed using RECIST v1.1 criteria for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.
Measured: From first occurrence of objective response to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
DOR as Determined by the Investigator RANO Criteria for Participants With LGG (Phase II)
Tumor assessment was performed using RANO criteria for Participants with LGG.
Measured: From first occurrence of objective response to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Overall Survival (OS) for Participants With Neuroblastoma (Phase I)
OS was defined as the time from initiation of study drug to death from any cause.
Measured: Baseline until death due to any cause (up to 5 years, 2 months)
OS for Participants With High-Grade Glioma (HGG) (Phase I) and Low-Grade Glioma (LGG) (Phase I and II)
OS was defined as the time from initiation of study drug to death from any cause. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.
Measured: Baseline until death due to any cause (up to 5 years, 2 months)
OS for Participants With All Other Tumours (Phase I)
OS was defined as the time from initiation of study drug to death from any cause.
Measured: Baseline until death due to any cause (up to 5 years, 2 months)
Maximum Plasma Concentration Observed (Cmax) of Cobimetinib
Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1. The sampling will allow determination of Cmax.
Measured: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21 (predose=within 4 hours prior to dose; cycle length=28 days)
Time to Cmax (Tmax) of Cobimetinib
Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1. The sampling will allow determination of Tmax.
Measured: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21 (pre-dose=within 4 hours prior to dose; cycle length=28 days)
Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of Cobimetinib
Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1. The sampling will allow determination of AUC0-24.
Measured: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21 (pre-dose=within 4 hours prior to dose; cycle length=28 days)
Apparent Clearance (CL/F) of Cobimetinib
Plasma samples for determination of Cobimetinib concentration were collected prior to dosing and at 2, 4, 6 and 24 hours after dosing on Days 1 and 21 of Cycle 1, and within 4 hours prior to dosing on Day 1 of Cycle 2.
Measured: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21; pre-dose on Cycle 2 Day 1 (pre-dose=within 4 hours prior to dose; cycle length=28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2015 (estimated)
- Study start20 May 2016
- Primary completion21 Jul 2021
- Study completion21 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02639546
- Sponsor's protocol ID
- GO29665
- Other IDs
- 2014-004685-25, 2014
- Acronym
- iMATRIXcobi
- Status last verified
- Sep 2022
- First submitted
- 3 Dec 2015
- Last updated
- 16 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 35715627
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02639546
- Acronym / sponsor ID
- iMATRIXcobi / GO29665
- Conditions
- Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 20 May 2016 (actual)
- Primary completion
- 21 Jul 2021 (actual)
- Study completion
- 21 Jul 2021 (actual)
- First posted
- 24 Dec 2015 (estimated)
- Results
- Posted 31 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Phase I (Tablet) Cobimetinib (0.6 mg/kg) | Experimental | Drug: CobimetinibDose-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. |
| Phase I (Tablet) Cobimetinib (0.8 mg/kg) | Experimental | Drug: CobimetinibDose-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. |
| Phase I (Tablet) Cobimetinib (1 mg/kg) | Experimental | Drug: CobimetinibDose-Escalation: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle. |
| Phase I (Suspension) Cobimetinib (0.6 mg/kg) | Experimental | Drug: CobimetinibDose-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. |
| Phase I (Suspension) Cobimetinib (0.8 mg/kg) | Experimental | Drug: CobimetinibDose-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. |
| Phase I (Suspension) Cobimetinib (1 mg/kg) | Experimental | Drug: CobimetinibDose-Escalation: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle. |
| Phase I (Suspension) Cobimetinib (1.33 mg/kg) | Experimental | Drug: CobimetinibDose-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. |
| Phase II (Suspension) Cobimetinib (1 mg/kg) | Experimental | Drug: CobimetinibDose-Expansion: Participants received 1 milligram per kilogram (mg/kg) cobimetinib orally once daily on Days 1 to 21 of each 28-day treatment cycle. |
Who may qualify
- Ages
- 6 months to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobimetinibAlso: RO5514041, GDC-0973, XL-518Cobimetinib tablet or suspension will be administered as per the schedule described in arm description. | Drug | Phase I (Suspension) Cobimetinib (0.6 mg/kg), Phase I (Suspension) Cobimetinib (0.8 mg/kg), Phase I (Suspension) Cobimetinib (1 mg/kg), Phase I (Suspension) Cobimetinib (1.33 mg/kg), Phase I (Tablet) Cobimetinib (0.6 mg/kg), Phase I (Tablet) Cobimetinib (0.8 mg/kg), Phase I (Tablet) Cobimetinib (1 mg/kg), Phase II (Suspension) Cobimetinib (1 mg/kg) |
Primary outcome
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Baseline up until 30 days after the last dose of study drug (up to 5 years, 2 months)
Dose-Limiting Toxicities (DLTs) were defined as cobimetinib-related adverse events occurring within the first 28 days of each administration of cobimetinib.
Percentage of Participants With Adverse Events (AEs), Including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Time frame: Baseline up until 30 days after the last dose of study drug (up to 5 years, 2 months)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs.
Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Cobimetinib
Time frame: Cycle 1 Day 1 up to Cycle 1 Day 28 (cycle length=28 days)
A prior dose level was defined as an MTD/MAD if at a certain dose level, there were greater than or equal to (>=) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs).
Percentage of Participants With Objective Response (Complete Response (CR) or Partial Response (PR)) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) for Participants With Neuroblastoma (Phase I)
Time frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment was performed using mINRC for Participants with Neuroblastoma.
Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RANO Criteria for Participants With High-Grade Glioma (HGG) (Phase I) and RECIST v1.1 for Participants With Low-Grade Glioma (LGG) (Phase I and II)
Time frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment was performed using Response Assessment in Neuro-Oncology (RANO) criteria for participants with HGG and Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.
Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RECIST v1.1 Criteria for Participants With All Other Tumours (Phase I)
Time frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment was performed using RECIST v1.1 for Participants with All Other Tumours.
Percentage of Participants With Objective Response (CR or PR) as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II)
Time frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment will be performed using RANO criteria for LGG.
Progression-Free Survival (PFS) as Determined by the Investigator Using mINRC for Participants With Neuroblastoma (Phase I)
Time frame: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment was performed using mINRC for Participants with Neuroblastoma.
PFS as Determined by the Investigator Using RANO Criteria for Participants With HGG (Phase I) and RECIST v1.1 for Partcipants With LGG (Phase I and II)
Time frame: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment was performed using RANO for participants with HGG and RECIST v1.1 for participants with LGG. While the data for LGG in the phase II cohort is presented separately in other parts of the record, it was also considered useful to combine the data for LGG from phase I and phase II, which was done here.
PFS as Determined by the Investigator Using RECIST v1.1 Criteria for Participants With All Other Tumours (Phase I)
Time frame: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment was performed using RECIST v1.1 for Participants with All Other Tumours.
PFS as Determined by the Investigator Using RANO Criteria for Participants With LGG (Phase II)
Time frame: From the time of cobimetinib study drug initiation to the first documented disease progression, or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Tumor assessment was performed using RANO criteria for Participants with LGG.
10 secondary outcomes
Recommended Phase II Dose (RP2D) of Cobimetinib
Time frame: Cycle 1 Day 1 up to Cycle 1 Day 28 (cycle length=28 days)
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 for Participants With LGG (Phase I and II)
Time frame: From first occurrence of objective response to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
DOR as Determined by the Investigator RANO Criteria for Participants With LGG (Phase II)
Time frame: From first occurrence of objective response to disease progression or death due to any cause, whichever occurs first (up to 5 years, 2 months)
Overall Survival (OS) for Participants With Neuroblastoma (Phase I)
Time frame: Baseline until death due to any cause (up to 5 years, 2 months)
OS for Participants With High-Grade Glioma (HGG) (Phase I) and Low-Grade Glioma (LGG) (Phase I and II)
Time frame: Baseline until death due to any cause (up to 5 years, 2 months)
OS for Participants With All Other Tumours (Phase I)
Time frame: Baseline until death due to any cause (up to 5 years, 2 months)
Maximum Plasma Concentration Observed (Cmax) of Cobimetinib
Time frame: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21 (predose=within 4 hours prior to dose; cycle length=28 days)
Time to Cmax (Tmax) of Cobimetinib
Time frame: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21 (pre-dose=within 4 hours prior to dose; cycle length=28 days)
Area Under the Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of Cobimetinib
Time frame: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21 (pre-dose=within 4 hours prior to dose; cycle length=28 days)
Apparent Clearance (CL/F) of Cobimetinib
Time frame: Pre-dose, 2, 4, 6, and 24 hours post-dose on Cycle 1 Days 1 and 21; pre-dose on Cycle 2 Day 1 (pre-dose=within 4 hours prior to dose; cycle length=28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35715627Trippett 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
17 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cobimetinib in people with Solid Tumors, run by Hoffmann-La Roche at 17 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, France, Spain, United Kingdom, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Baseline up until 30 days after the last dose of study drug (up to 5 years, 2 months)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02639546, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2022.