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

NCT04222413 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 20002320-C-0023
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Colorectal Neoplasms; Advanced Solid Tumors; Pediatric Solid Tumor; Advanced Breast Cancer; Malignant Peripheral Nerve Sheath Tumor; Metastatic Pancreatic Cancer

Keywords

First-In-Class Investigational Agent; Peri-Nucleolar Compartment (PNC); effective therapies against metastasis; Oral Administration; Maximum Recommended Starting Dose

Outcome Measures

Primary Outcomes (2)

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

  MTD of metarrestin

  28 days

• 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

  every 2 months

Secondary Outcomes (7)

• 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

  every 2 months

• To determine plasma PK levels of metarrestin in humans

  28 days

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

  at progression

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

  at progression

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

  28 days after treatment discontinuation

Study Arms (2)

1/Arm 1

EXPERIMENTAL

Escalating/de-escalation doses of metarrestin

Drug: Metarrestin

2/Arm 2

EXPERIMENTAL

MTD of metarrestin

Drug: Metarrestin

Interventions

Metarrestin DRUG

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

1/Arm 1; 2/Arm 2

Eligibility Criteria

• Age: 12 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (\>= 18 years) subjects with:
• histologically or cytologically confirmed solid tumors (Phase IA).
• histologically or cytologically confirmed pancreatic, colorectal, or breast cancer (Phase IB)
• 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
• 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,

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

University of Kansas

Fairway, Kansas, 66205, United States

RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pancreatic Neoplasms; Neurofibrosarcoma; Colorectal Neoplasms

Interventions

metarrestin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Udo Rudloff, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Murielle Hogu

CONTACT

(240) 858-3335; murielle.hogu@nih.gov

Udo Rudloff, M.D.

CONTACT

(240) 760-6238; rudloffu@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 10, 2020
• Study Start: October 27, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 24, 2026

Record last verified: 2025-09-30

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (2)