A Study of Cobimetinib in Pediatric and Young Adult Patients with Previously Treated Solid Tumors
- Conditions
- Solid TumorsMedDRA version: 19.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004685-25-FR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 56
- Signed informed consent form or child's informed assent, when appropriate as determined by patient's age and individual site and country standards
- Age >=6 years to <18 years (dose-escalation stage) and >=6 years to <30 years (expansion stage)
- Able to comply with the study protocol, in the investigator’s judgment
- Tumor for which prior treatment has proven to be ineffective (i.e.,
relapsed or refractory) or intolerable or for which no standard therapy exists.
- Tumors 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
-Tumors from the following groups that in the judgment of the investigator are life threatening, resulting in severe symptoms, or are in close proximity to vital structures:
-NF1-associated tumors (including plexiform neurofibroma)
-Schwannoma
-Any solid tumor or brain tumor that occurs in a patient with a RASopathy (such as NF1 or Noonan syndrome)
-Rhabdoid tumors, including atypical teratoid/rhabdoid tumor
Any solid or brain tumor that has been molecularly profiled and shown to have RAS/RAF/MEK/ERK pathway activation, with approval of the Medical Monitor.
- Tumor diagnosis must be histologically or cytologically confirmed either at the time of diagnosis or at the time of relapse, except in the following scenario:
-DIPG does not require histologic confirmation if radiographic findings are sufficient to make diagnosis and institutional standard of care does not mandate biopsy for diagnosis.
- Current disease state for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Disease that is measurable as defined by International Neuroblastoma Response Criteria (INRC), Response Assessment in Neuro-Oncology (RANO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers, or other reliable measures
- Availability of tumor tissue at study enrollment is mandatory. Archival tumor tissue block or 15 freshly cut unstained, serial slides available for submission, and/or willingness to undergo a core or excisional biopsy prior to enrollment
- Lansky Performance Status or Karnofsky Performance Status >=50%
- Life expectancy >=3 months, in the investigator's judgment
- Adequate hematologic and end organ function, defined by the following laboratory results obtained within 28 days prior to initiation of study drug:
-Absolute neutrophil count (ANC) >= 0.75 × 10 exp9/L (unsupported)
-Platelet count >=75 × 10 exp9/L (unsupported)
-Hemoglobin >=8 gram/deciliter (g/dL) (transfusion is acceptable to meet this criterion)
-Bilirubin <=1.5 × upper limit of normal (ULN) for age
-Aspartate aminotransferase (AST) and alanine transaminase (ALT) <=2.5 × ULN for age
-Serum creatinine <=1.5 × ULN for age or creatinine clearance (or radioisotope glomerular filtration rate) > 70 milliliter per minute (mL/min) /1.73 meter exp2/m
- Fractional shortening (FS) >= 30% and left ventricular ejection fraction (LVEF) >= 50% at baseline, as determined by echocardiography within 28 days prior to initiation of study drug
- Female
- Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) within 3 months prior to initiation of study drug
- Treatment with thoracic or mediastinal radiotherapy within 6 weeks prior to initiation of study drug
- Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, or herbal cancer therapy within 4 weeks or < 5 half-lives, whichever is shorter, prior to initiation of study drug
- Treatment with a long-acting hematopoietic growth factor within 2 weeks prior to initiation of study drug or a short-acting hematopoietic growth factor within 1 week prior to initiation of study drug
- Treatment with investigational therapy (with the exception of cancer therapies as described above) within 4 weeks prior to initiation of study drug
- Requirement for initiation of corticosteroids or an increase in the dose of corticosteroids within 1 week prior to initiation of study drug
- Treatment with St. John's wort or hyperforin or drugs that are strong inhibitors or inducers of CYP within 1 week prior to initiation of study drug
- Ingestion of grapefruit juice within 1 week prior to initiation of study drug
- Any toxicity (excluding alopecia) from prior treatment that has not resolved to Grade <= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) at screening except as permitted in the exclusion criteria
- 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. Placement of a vascular access device or minor surgery is permitted if the site has healed prior to initiation of study drug
- Known active infection (excluding fungal infection of the nail beds) within 28 days prior to initiation of study drug that has not completely resolved
- History or evidence of retinal pathology on ophthalmologic examination that is considered to be a risk factor for or indicative of neurosensory retinal detachment, Central Serous Chorioretinopathy (CSCR), neovascular retinopathy, or retinopathy of prematurity
- Known hypersensitivity to any component of the study drug
- Inability to swallow tablets
- Impaired gastrointestinal absorption
- Prior allogenic bone marrow transplantation or prior solid organ transplantation
- Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications
- Current drug or alcohol use or dependence that would interfere with adherence to study requirements, in the opinion of the investigator
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method