Savolitinib in Treating Patients With Recurrent or Refractory Primary CNS Tumors

Running, not enrolling · Phase 1

Conditions studied: Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Malignant Glioma, Recurrent Medulloblastoma, Recurrent Primary Central Nervous System Neoplasm, Refractory Diffuse Intrinsic Pontine Glioma, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Primary Central Nervous System Neoplasm

In brief

This phase I trial studies the side effects and best dose of savolitinib in treating patients with primary central nervous system (CNS) tumors that have come back (recurrent) or does not respond to treatment (refractory). Savolitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID

NCT03598244

Run by

National Cancer Institute (NCI)

People needed

41

Starts

2018-11-27

Expected to finish

2027-05-27

Last updated by the study team

2026-07-30

Who can join

Age: 6 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients with a histologically confirmed diagnosis of a primary CNS tumor (medulloblastoma, high-grade glioma, or diffuse intrinsic pontine glioma [DIPG]) that is recurrent, refractory, or progressive. All tumors must have histologic verification at either the time of diagnosis or recurrence except patients with diffuse intrinsic brain stem tumors. These patients must have radiographic or clinical evidence of progression. Patients with a recurrent, progressive, or refractory primary CNS tumor with evidence of genetic activation of the MET pathway, regardless of histology, are also eligible to the Phase I component of this study
• Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI imaging that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment
• Efficacy Expansion Cohort: Patients must have a recurrent, progressive, or refractory primary CNS tumor with evidence of genetic activation of the MET pathway, regardless of histology. Specimens can be from diagnosis or recurrence and there is no time limit from when the specimen was obtained prior to enrollment onto the efficacy expansion cohort. Results from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory will be accepted for this eligibility criterion. Sites must provide a redacted copy of the local CLIA-certified sequencing laboratory report to the study chair via email prior to enrollment. MET pathway activation is defined as:
• MET mutations, OR
• MET or HGF amplification, OR
• MET fusion
• Recurrent or refractory primary malignant CNS tumor patients must have adequate pre-trial frozen or formalin-fixed paraffin-embedded (FFPE) tumor material available for the required correlative studies. If target amounts of tissue or number of slides are not available, the site must obtain study chair/co-chair approval for adequacy of submitted tumor samples and prioritization of studies to be performed, prior to patient enrollment
• Patients with DIPG who have pre-trial tumor tissue available are requested to submit tissue; however, this is not required for eligibility
• Patients must have evaluable disease to be eligible. Evaluable disease is defined as the presence of at least one lesion that can be measured accurately in at least 2 (two) dimensions
• Patients must be > 5 years and =< 21 years of age at the time of study enrollment
• Body surface area (BSA)
• Patients enrolled on 75 mg/m\^2/day (dose level 0) must have a BSA >= 1.00 m\^2
• Patients enrolled on 150 mg/m\^2/day (dose level 1) must have a BSA >= 0.55 m\^2
• Patients enrolled on 240 mg/m\^2/day (dose level 2) must have a BSA >= 0.67 m\^2
• Patients enrolled on 350 mg/m\^2/day (dose level 3) must have a BSA >= 0.73 m\^2
• Patients must have failed prior standard therapy for their tumor. Patients with medulloblastoma must have received radiation therapy in addition to platinum and alkylator-based chemotherapy. Patients with high-grade glioma (HGG) and DIPG must have at least received radiation therapy. Patients must have recovered from the acute treatment related toxicities (defined as =< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study
• Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if it included nitrosourea
• Biologic or investigational agent (anti-neoplastic):
• Patients must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment
• For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Monoclonal antibody treatment and agents with known prolonged half-lives:
• Patients must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent >= 28 days prior to study enrollment
• Patients must have had their last fraction of:
• Craniospinal irradiation or total body irradiation or radiation to >= 50% of pelvis > 12 weeks prior to enrollment
• Focal irradiation > 4 weeks prior to enrollment

You may not qualify if…

• Pregnant women or nursing mothers are excluded from this study. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Pregnant women are excluded from this study because there are unknown but potential risks to an unborn baby from savolitinib. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with savolitinib, breastfeeding should be discontinued if the mother is treated with savolitinib
• Patients with a known serious active infection including, but not limited to human immunodeficiency virus, and tuberculosis
• Patients with a known active or resolved viral hepatitis infection
• Patients with any clinically significant unrelated systemic illness or significant cardiac, pulmonary, hepatic, or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
• Patients with uncontrolled hypertension (i.e., a blood pressure [BP] > 95th percentile for age, height, and sex, patients with values above these levels must have their blood pressure controlled with medication prior to starting study drug)
• The normal blood pressure by height, age, and sex can be assessed by using the NIH Guidelines on the PBTC Member's website (Protocols- Generic Forms and Templates- Normal Blood Pressure by Height and Age)
• Patients with any of the following cardiac diseases
• Congestive heart failure (New York Heart Association >= grade 2)
• Clinically significant cardiac arrhythmia
• Mean resting corrected QT interval (QTc Bazett) > 450 msec on screening obtained from 3 electrocardiograms (EKGs) or
• Factors that may increase the risk of QTc prolongation such as chronic hypokalemia not correctable with supplements, congenital or familial long QT syndrome, or
• Family history of unexplained sudden death under 40 years of age in first-degree relatives or
• Any concomitant medication known to prolong the QT interval and cause Torsade de Pointes. These drugs must have been discontinued prior to the start of administration of study treatment in accordance with guidance
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting EKG, e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec
• Patients with history of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement, with or without normal liver function tests (LFTs), including but not limited to:
• Hemochromatosis
• Alpha -1 antitrypsin deficiency
• Autoimmune hepatitis (AIH)
• Primary sclerosing cholangitis (PSC)
• Primary biliary cirrhosis (PBC)
• Biopsy-confirmed non-alcoholic steatohepatitis (NASH) with advanced fibrosis
• Biopsy-confirmed alcoholic steatohepatitis with advanced fibrosis
• Wilson's disease
• Hepatocellular carcinoma
• Patients with liver metastases are eligible, provided they meet other eligibility criteria, including liver biochemistry criteria

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Nationwide Children's Hospital — Columbus, Ohio, United States
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
• Texas Children's Hospital — Houston, Texas, United States
• Hospital for Sick Children — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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