Neoplasms

Digestive System Diseases

All Conditions

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Nervous System Diseases

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Gastrointestinal Diseases

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Peripheral Nervous System Diseases

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Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Neurofibromatoses

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Neurofibromatosis

Escalating/de-escalation doses of metarrestin

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

Metarrestin

Murielle Hogu

Udo Rudloff, M.D.

Joaquina Baranda, MD

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

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.

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

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

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

Fraction of objective responses determined and reported as the ORR

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

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

Median amount of time subject survives without disease progression after treatment

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

The fraction of patients who can tolerate the dose

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors	NCT04222413	Advanced Solid ... Metastatic Panc... Pediatric Solid... Advanced Breast... Malignant Perip... Colorectal Neop...	Metarrestin	12 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors	NCT04222413	Advanced Solid ... Metastatic Panc... Pediatric Solid... Advanced Breast... Malignant Perip... Colorectal Neop...	Metarrestin	12 Years - 120 Years	National Institutes of Health Clinical Center (CC)

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