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
National Cancer Institute (NCI)
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.
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 t…
Eligibility
- Age range
- 12–120 years
- Sex
- All
- Healthy volunteers
- No
* 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…
Interventions
- DrugMetarrestin
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
Locations (2)
- University of KansasFairway, Kansas
- National Institutes of Health Clinical CenterBethesda, Maryland