Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors

Recruiting now · Phase 1

Conditions studied: Advanced Solid Tumors, Metastatic Pancreatic Cancer, Pediatric Solid Tumor, Advanced Breast Cancer, Malignant Peripheral Nerve Sheath Tumor, Colorectal Neoplasms

In brief

Background: Metastasis is the spread of cancer from one organ to a nonadjacent organ. It causes 90% of cancer deaths. No treatment specifically prevents or reduces metastasis. Researchers hope a new drug can help. It stops cancer cells from growing and spreading further and possibly shrink cancer lesions in distant organs. Objective: To find a safe dose of metarrestin and to see if this dose shrinks tumors. Eligibility: Adults age 18 and older with pancreatic cancer, breast cancer, or a solid tumor that has not been cured by standard therapies. Also, children age 12-17 with a solid tumor (other than a muscle tumor) with no standard therapy options. Design: Participants will be screened with: * blood tests * physical exam * documentation of disease confirmation or tumor biopsy * electrocardiogram to evaluate the heart * review of their medicines and their ability to do their normal activities Participants will take metarrestin by mouth until they cannot tolerate it or stop to benefit from it. They will keep a medicine diary. Participants will visit the Clinical Center. During the first month there are two brief hospital stays required with visits weekly or every other week thereafter. They will repeat some of the screening tests. They will fill out questionnaires. They will have tests of their cognitive function. They will have an electroencephalogram to record brain activity. They will have a computed tomography (CT) scan or magnetic resonance imaging (MRI). A CT is a series of X-rays of the body. An MRI uses magnets and radio waves to take pictures of the body. Adult participants may have tumor biopsies. Participants will have a follow-up visit 30 days after treatment ends. Then they will have follow-up phone calls or emails every 6 months for the rest of their life or until the study ends.

Key facts

Study ID

NCT04222413

Run by

National Cancer Institute (NCI)

People needed

116

Starts

2020-10-27

Expected to finish

2028-12-31

Last updated by the study team

2026-08-04

Who can join

Age: 12 and older, up to 120. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Anticancer treatment within designated period before treatment initiation including:
• minor surgical procedure (such as biliary stenting) within 14 days. Note: if liver function tests after biliary stenting or renal function tests after ureteral stenting return to normal, within 5 days after biliary or ureteral stenting;
• major surgical procedure or curative radiation treatment within 28 days;
• palliative radiation treatment within 14 days;
• chemotherapy or experimental drug treatment with published half-life known to be 72 hours or less within 14 days;
• experimental drug treatment with unpublished or half-life greater than 72 hours within 28 days;
• chemotherapy regimen containing an alkylating antineoplastic agent (cyclophosphamide, chlorambucil, melphalan, or ifosfamide), alkylating-like (platinumbased chemotherapeutic drugs, platinum analogues), and non-classical alkylating agent (dacarbazine, temozolomide) within 28 days.
• Patients receiving any medications or substances that are moderate and strong inhibitors or inducers of CYP3A4 and are not able to safely stop these medications are excluded from this study; patients must stop strong CYP3A4 inhibiting/inducing medications within 5 published half-lives and moderate within 3 published half-lives prior to the treatment initiation.
• Note: dihydropyridine calcium - channel blockers are permitted for management of underling disease
• Subjects with cardiomyopathy diagnosed within 6 months prior to treatment initiation including but not limited to the following:
• hypertrophic cardiomyopathy
• arrhythmogenic right ventricular cardiomyopathy
• abnormal ejection fraction (echocardiogram [ECHO]) <= 53% (if a range is given then the upper value of the range will be used)
• previous moderate or severe impairment of left ventricular systolic function (LVEF <45%)
• severe valvular heart disease
• atrial fibrillation with a ventricular rate >100 bpm on EKG at rest
• Fridericia's corrected QT interval (QTcF) >= 480 msec (adults) or >= 460 msec (pediatric subjects, aged 12 to <18 years) or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome.
• HIV, HCV, HBV positive patients on antiviral drugs are excluded due to the absence of previous experience with concurrent use of antiviral medications and the investigational drug product to be evaluated in the current study and possible for adverse pharmacokinetic and/or pharmacodynamic interactions.
• Previous malignant disease (other than the target malignancy to be investigated in this trial) within the last 3 years. Note: subjects with a history of cervical carcinoma in situ, superficial or non-invasive bladder cancer, or basal cell or squamous cell carcinoma in situ previously treated with curative intent are NOT excluded.
• Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures.
• Subjects with central nervous system (CNS) metastases or CNS disorders known to increase possible neurotoxicity of metarrestin in case of compromised blood-brain barrier (e.g. recent stroke (<3 months of treatment initiation), infectious causes).
• Significant acute or chronic infections including tuberculosis with presence of clinical symptoms or physical findings.
• Patients with a history of any seizures or increased risk of seizures on screening EEGs defined by 1) interictal epileptiform discharges, 2) temporal intermittent rhythmic delta activity (TIRDA), or 3) electrographic or clinical seizures on EEG.
• Clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial.
• Patients with previous gastric bypass, patients receiving nutrition via feeding tubes or parenterally, or patients with malabsorptive conditions (damage to the intestine from infection, inflammation, trauma, or surgery, celiac disease, Crohn's disease, chronic pancreatitis, or cystic fibrosis resulting malabsorption). Patients with refractory nausea and vomiting. Note: patients with gastric banding are allowed.

Where it is running

• University of Kansas — Fairway, Kansas, United States (enrolling)
• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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