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Advanced Solid TumorsPhase 1NCT04222413

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

A Phase 1 study testing Metarrestin in people with Advanced Solid Tumors and Metastatic Pancreatic Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 12 to 120 years
What is being tested?
Metarrestin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
116 participants
Where
2 sitesUnited States
Study dates
27 Oct 2020to 31 Dec 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 120 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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;
Show all 26Show fewer
  • 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.
  • Pregnant individuals.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Murielle Hogu contact

(240) 858-3335

murielle.hogu@nih.gov

Udo Rudloff, M.D. contact

(240) 760-6238

rudloffu@mail.nih.gov

United States2 sites, 2 recruiting

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

    For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, 888-624-1937

    Recruiting

  • University of Kansas

    Fairway, Kansas, 66205

    Joaquina Baranda, MD, 913-588-4709, jbaranda@kumc.edu

    Recruiting

Other trials in United States

About this study

Official title: 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

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.

Read more

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.

Read the detailed description

Background:

Metarrestin is a first-in-class investigational agent targeting the peri-nucleolar compartment (PNC), a marker of genome organization associated with metastasis.

Preclinical studies have shown that metarrestin effectively suppresses metastasis and extends overall survival in different cancer models.

Multi-species allometric scaling and good laboratory practice (GLP) toxicology and toxicokinetic studies indicate that metarrestin administered at a calculated safe maximum recommended starting dose (MRSD) to human subjects is predicted to afford intratumoral exposure levels within the therapeutic range observed preclinically.

Objectives:

Phase IA: To determine the maximum tolerated dose (MTD) of metarrestin.

Phase IB: To determine the Objective Response Rate (ORR) according to Evaluation Criteria (RECIST 1.1) in patients treated with metarrestin at the MTD.

Eligibility:

Adult subjects with any advanced solid tumors (Cohort IA), or pancreatic, colorectal, or breast tumors (Cohort IB1).

OR

Pediatric subjects age 12 and older with solid tumors other than rhabdomyosarcoma (RMS) including embryonal, alveolar, spindle cell/sclerosing, and pleomorphic subtypes of RMS (Cohort IB2).

Patients must have progressed on prior standard chemotherapeutic therapy.

Design:

This is first-in-human Phase I trial to investigate the safety and clinical activity of metarrestin in subjects with metastatic solid tumors.

During Phase IA MTD of metarrestin will be estimated in adult patients with solid tumors.

During Phase IB adult patients with breast, colorectal, or pancreatic cancer, and pediatric patients with solid organ cancer will be treated at dose level of estimated MTD.

Patients will receive treatment in cycles consisting of 28 (+7/- 2) days.

Metarrestin will be administered PO until progression or unacceptable toxicity.

Being tested
Metarrestin
Keywords
First-In-Class Investigational Agent, Peri-Nucleolar Compartment (PNC), effective therapies against metastasis, Oral Administration, Maximum Recommended Starting Dose
Medical subject headings
Pancreatic Neoplasms, Neurofibrosarcoma, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetarrestinDrug

    Phase IA: Loading dose on Day 1 of Cycle 1 for Dose Levels 1-7. Loading dose on Days 1 and 3 of Cycle 1 for Dose Levels 8-11. After the loading dose on Day 1 or Days 1 and 3 of Cycle 1, continue on Mondays-Wednesdays-Fridays of every following cycle. Phase IB: PO according to the dose and schedule estimated during Phase IA

Study groups in NCT04222413
Study groupRoleWhat they receive
1/Arm 1ExperimentalEscalating/de-escalation doses of metarrestin
Receives: Drug: Metarrestin
2/Arm 2ExperimentalMTD of metarrestin
Receives: Drug: Metarrestin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To identify the maximum tolerated dose (MTD) of metarrestin in subjects with metastatic solid tumors

    MTD of metarrestin

    Measured: 28 days

  2. To determine the Objective Response Rate (ORR) according to Evaluation Criteria (RECIST 1.1) in patients treated with metarrestin at the MTD

    Fraction of objective responses determined and reported as the ORR

    Measured: every 2 months

Secondary outcomes (7)

  1. To determine the Objective Response Rate (ORR) according to Evaluation Criteria (RECIST 1.1) in patients treated with metarrestin at the MTD in Cohort IB1

    The ORR rate will be determined by dividing the number of patients with an objective response by the number of evaluable patients who are treated at the MTD for cohort Phase IB1

    Measured: every 2 months

  2. To determine plasma PK levels of metarrestin in humans

    The pharmacokinetic (PK) profile of metarrestin will be derived from single dose and multiple dose PK measures for each dose level collecting the standard pharmacokinetic parameters

    Measured: 28 days

  3. To assess progression-free survival (PFS) according to RECIST 1.1

    Median amount of time subject survives without disease progression after treatment

    Measured: at progression

  4. To determine duration of overall response (DOR) rate according to Response Evaluation Criteria (RECIST 1.1) in subjects with metastatic solid tumors

    Kaplan-Meier curves beginning at the date of response will be used and will be determined in all responding patients treated on the Phase IB expansion cohorts

    Measured: at progression

  5. To determine tolerability of the adult recommended dose in children >= 12 year of age (Cohort IB2)

    The fraction of patients who can tolerate the dose

    Measured: 28 days after treatment discontinuation

  6. To assess safety and tolerability of metarrestin (Cohort IB1)

    All treatment-related AEs will be captured, and for each grade, the number and type of AE per dose level will be descriptively described in Cohort 1B1

    Measured: 28 days after treatment discontinuation

  7. To assess safety and tolerability of metarrestin in subjects with metastatic solid tumors

    All treatment-related AEs will be captured, and for each grade, the number and type of AE per dose level will be descriptively described

    Measured: 28 days after treatment discontinuation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2020
  2. Study start27 Oct 2020
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
116 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04222413
Sponsor's protocol ID
200023
Other IDs
20-C-0023
Status last verified
13 Oct 2026
First submitted
7 Jan 2020
Last updated
16 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Metarrestin in people with Advanced Solid Tumors and Metastatic Pancreatic Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Murielle Hogu ((240) 858-3335, murielle.hogu@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To identify the maximum tolerated dose (MTD) of metarrestin in subjects with metastatic solid tumors (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04222413.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.

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Clinical Trial NCT04222413 | AzTrials