A Study of Cobimetinib in Pediatric and Young Adult Patients with Previously Treated Solid Tumors

Phase 1

• Conditions: Solid Tumors; MedDRA version: 20.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000020962; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004685-25-NL
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-15
• Last Update Posted: 26 July 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

- Signed informed consent form or child's informed assent, when appropriate as determined by patient's age and individual site and country standards
- For dose-escalation stage, tablets: age >=6 years to <18 years; dose-escalation stage, suspension: age >=6 months to < 18 years
- For expansion stage: age >=6 months (>=6 years if suspension is not available to <30 years
- Able to comply with the study protocol, in the investigator’s judgment
- Histologically or cytologically confirmed tumor from the list below, but not limited to, for which prior treatment has proven to be ineffective (i.e., relapsed or refractory) or intolerable or for which no standard therapy exists. Tumor with known or expected RAS/RAF/MEK/ERK pathway involvement. Patients must have had histologic or cytologic confirmation of malignancy at the time of diagnosis or relapse:
• Gliomas, including high- and low-grade gliomas, and diffuse intrinsic pontine glioma (DIPG)
• Soft tissue sarcomas, including rhabdomyosarcoma
• Neuroblastoma
• Melanoma
• Neurofibromatosis (NF)-associated tumors (including plexiform neurofibroma, malignant peripheral nerve sheath tumors, and schwannoma)
• Any solid tumor or brain tumor that occurs in a patient with a RASopathy (such as NF1 or Noonan syndrome)
• Rhabdoid tumors, including anaplastic teratoid/rhabdoid tumor (ATRT)
• Any solid or brain tumor that has been molecularly profiled and shown to have RAS/RAF/MEK/ERK pathway activation, with approval of Medical Monitor
- 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 the modified International Neuroblastoma Response Criteria (mINRC), 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 × 10^9/Liter (L) (unsupported)
• Platelet count >=75 × 10^9/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 (m)^2
- 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
- Must be able to swallow liquid suspension
- Female patients of childbearing potential and male patients with a female partner of childbearing potential must agree with the required contraceptive methods as defined in the protocol

Are the

Exclusion Criteria

- Prior treatment with cobimetinib or other MEK inhibitor. Prior sorafenib use is permissible
- Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) within 3 months prior to initiation of study drug
- Treatment with chemotherapy or differentiation therapy or immunotherapy within 4 weeks prior to initiation of study drug or, if treatment included nitrosoureas, within 6 weeks 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 CYP3A 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 and ototoxicity) 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 of Grade = 2 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
- For brain tumor patients, use of anticoagulants within 1 week of study drug initiation
- 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 oral medications
- 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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified