NCT04222413RecruitingPhase 1

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

First-in-Human Phase I Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors

Source: ClinicalTrials.gov · Last updated 2 Nov 2026

Brief summary (registry, in English)

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.

Status (registry): Recruiting
Phase (registry): Phase 1
Study type: Interventional
Enrollment: 116 (estimated)
First submitted: 7 Jan 2020
Start date: 27 Oct 2020
Primary completion date: 31 Dec 2027
Lead sponsor: National Cancer Institute (NCI)
Diseases: Pancreatic cancer, Metastatic breast cancer, Colorectal cancer, Childhood cancers, Sarcoma
NCT number: NCT04222413

What you commit to

Study type: Interventional · Phase 1
Planned participants: 116
From 27 Oct 2020 to the primary completion date, 31 Dec 2027
2 sites in 1 country
Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

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 medications known to carry a high to moderate risk to lower seizure threshold within 2 weeks prior to treatment initiation.
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.
Patients with a history of any seizures within 1 year prior to the study treatment initiation 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. Note: Patients with brain metastasis are eligible providing that patients had no seizures or clinical signs of central nervous system (CNS) disease-related neurotoxicity (ataxia, sensory, cognitive changes) within 1 year prior to the study treatment initiation and baseline EEG shows no changes indicative of increased seizure risk.
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.

Other illness

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.
Significant acute or chronic infections including tuberculosis with presence of clinical symptoms or physical findings.
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.

Lab values

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.

Other

Pregnant individuals.

Criteria the registry did not label

INCLUSION CRITERIA:
Adult (\>= 18 years) subjects with:
- histologically or cytologically confirmed solid tumors (Phase IA).
- OR
- --histologically or cytologically confirmed pancreatic, colorectal, or breast cancer (Phase IB)
- OR
Pediatric (\>=12 and \< 18 years) subjects with histologically or cytologically confirmed solid tumors other than rhabdomyosarcoma (RMS) including embryonal, alveolar, spindle cell/sclerosing, and pleomorphic subtypes of RMS (Phase IB).
Subjects must have disease that:
- is not amenable to potentially curative resection,
- spread at least to one other organ system other than primary tumor or recurred after removal of primary tumor,
- has site measurable per RECIST 1.1 (Phase IB only).
- progressed on or after at least one line of standard systemic chemotherapy (Phase IA and IB1)
- have no standard therapy option available (Phase IB2)
Patients must have recovered from any acute toxicity related to prior therapy or surgery or disease to a grade 1 or less.
Performance status
- Karnofsky \>= 70% (for patients \>= 16 years old), Lansky \>= 70% (for patients \<16 years old)
Adequate hematological function defined by:
- absolute neutrophil count (ANC) \>= 1.0 x 10(9)/L,
- transfusion-independent platelet count \>= 100 x 10(9)/L,
- Hgb \>= 9 g/ dL (patients who have received \<= 2 PRBC transfusions within 48 hours are eligible)
Adequate coagulation as defined by:
- --INR\<1.5 (or \< 3.0 if subjects are currently taking anticoagulated medications) Note: increase of the upper limit of INR is restricted only to subjects who are receiving anticoagulation for medical reasons (DVT/PE prophylaxis, treatment for a thromboembolic event) and have increased INR because of these medications. Patients who have an elevated INR due to compromised liver function or any other medical conditions remain excluded
Adequate hepatic function defined by:
- --a total bilirubin level \<= 1.5 x ULN, (total bilirubin \<= 2.0 x ULN in case of prior diagnosis of Gilbert syndrome)
- an AST level \<= 3xULN
- an ALT level \<= 3 xULN
Adequate renal function defined by:
- --Creatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl)\*
- ---\< 1.5x institution upper limit of normal OR
- ---\>= 45 mL/min/1.73 m\^2 for participant with creatinine levels \>= 1.5 X institutional ULN
- \*Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.
The effects of the study treatment on the developing human fetus are unknown; thus, individuals of childbearing potential and individuals who can father children must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior
- to study entry, for the duration of study therapy and up to 120 days after the last dose of the study drug.
Nursing participants must be willing to discontinue nursing at the time of the study treatment initiation.
Weight: \>= 35 kg (\>= 18 years old) or \>=40 kg (\>= 12 and \< 18 years old).
Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document.
Subjects must have lesion(s) accessible for biopsy (other than used for measurement of disease) and be willing to undergo mandatory study biopsies (Cohort IB1 only).
Ability to swallow oral capsules.

Age in the registry: 12 years to 120 years · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (2)

Sites in registry order. Pick your city on the disease page to sort them by distance.

Site	City	Country	Site status
National Institutes of Health Clinical Center Coordinator of this site? Confirm its status	Bethesda	United States	Recruiting
University of Kansas Coordinator of this site? Confirm its status	Fairway	United States	Recruiting

This page is information, not medical advice. Discuss any trial with your doctor.