Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors
- Conditions
- Metastatic Pancreatic CancerPediatric Solid TumorAdvanced Breast CancerMalignant Peripheral Nerve Sheath TumorColorectal NeoplasmsAdvanced Solid Tumors
- Interventions
- Registration Number
- NCT04222413
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 98
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 2/Arm 2 Metarrestin MTD of metarrestin 1/Arm 1 Metarrestin Escalating/de-escalation doses of metarrestin
- Primary Outcome Measures
Name Time Method To identify the maximum tolerated dose (MTD) of metarrestin in subjects with metastatic solid tumors 28 days MTD of metarrestin
To determine the Objective Response Rate (ORR) according to Evaluation Criteria (RECIST 1.1) in patients treated with metarrestin at the MTD every 2 months Fraction of objective responses determined and reported as the ORR
- Secondary Outcome Measures
Name Time Method 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 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
To assess progression-free survival (PFS) according to RECIST 1.1 at progression Median amount of time subject survives without disease progression after treatment
To determine plasma PK levels of metarrestin in humans 28 days 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
To determine duration of overall response (DOR) rate according to Response Evaluation Criteria (RECIST 1.1) in subjects with metastatic solid tumors at progression 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
To determine tolerability of the adult recommended dose in children = 12 year of age (Cohort IB2) 28 days after treatment discontinuation The fraction of patients who can tolerate the dose
To assess safety and tolerability of metarrestin (Cohort IB1) 28 days after treatment discontinuation 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
To assess safety and tolerability of metarrestin in subjects with metastatic solid tumors 28 days after treatment discontinuation All treatment-related AEs will be captured, and for each grade, the number and type of AE per dose level will be descriptively described
Trial Locations
- Locations (2)
University of Kansas
🇺🇸Fairway, Kansas, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States