RECRUITING

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

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Conditions

Advanced Solid TumorsMetastatic Pancreatic CancerPediatric Solid TumorAdvanced Breast CancerMalignant Peripheral Nerve Sheath TumorColorectal NeoplasmsFirst-In-Class Investigational AgentPeri-Nucleolar Compartment (PNC)effective therapies against metastasisOral AdministrationMaximum Recommended Starting Dose

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2020-10-27
Study Completion:2028-12-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04222413

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 120 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Adult (\>= 18 years) subjects with:
  2. * histologically or cytologically confirmed solid tumors (Phase IA).
  3. * 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).
  4. * Subjects must have disease that:
  5. * is not amenable to potentially curative resection,
  6. * spread at least to one other organ system other than primary tumor or recurred after removal of primary tumor
  7. * has site measurable per RECIST 1.1
  8. * progressed on or after at least one line of standard systemic chemotherapy (Phase IA and IB1)
  9. * have no standard therapy option available (Phase IB2)
  10. * Patients must have recovered from any acute toxicity related to prior therapy or surgery or disease to a grade 1 or less.
  11. * Performance status
  12. * Adequate hematological function defined by:
  13. * absolute neutrophil count (ANC) \>= 1.0 x 10(9)/L,
  14. * transfusion-independent platelet count \>= 100 x 10(9)/L,
  15. * Hgb \>= 9 g/ dL (patients who have received \<= 2 PRBC transfusions within 48 hours are eligible)
  16. * Adequate coagulation as defined by:
  17. * Adequate hepatic function defined by:
  18. * a total bilirubin level \<= 1.5 x ULN, (total bilirubin \<= 2.0 x ULN in case of prior diagnosis of Gilbert syndrome)
  19. * an AST level \<= 3xULN
  20. * an ALT level \<= 3 xULN
  21. * Adequate renal function defined by:
  22. * Creatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl)
  23. * Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.
  24. * 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
  25. * Nursing participants must be willing to discontinue nursing at the time of the study treatment initiation.
  26. * Weight \>= 35 kg.
  27. * Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document.
  28. * 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).
  29. * Ability to swallow oral capsules.
  1. * Anticancer treatment within designated period before treatment initiation including:
  2. * 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;
  3. * major surgical procedure or curative radiation treatment within 28 days;
  4. * palliative radiation treatment within 14 days;
  5. * chemotherapy or experimental drug treatment with published half-life known to be 72 hours or less within 14 days;
  6. * experimental drug treatment with unpublished or half-life greater than 72 hours within 28 days;
  7. * 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.
  8. * 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.
  9. * Subjects with cardiomyopathy diagnosed within 6 months prior to treatment initiation including but not limited to the following:
  10. * hypertrophic cardiomyopathy
  11. * arrhythmogenic right ventricular cardiomyopathy
  12. * abnormal ejection fraction (echocardiogram \[ECHO\]) \<= 53% (if a range is given then the upper value of the range will be used)
  13. * previous moderate or severe impairment of left ventricular systolic function (LVEF \<45%)
  14. * severe valvular heart disease
  15. * atrial fibrillation with a ventricular rate \>100 bpm on EKG at rest
  16. * 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.
  17. * 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.
  18. * 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.
  19. * Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures.
  20. * 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).
  21. * Significant acute or chronic infections including tuberculosis with presence of clinical symptoms or physical findings.
  22. * 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.
  23. * 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.
  24. * 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.
  25. * Pregnant individuals.

Contacts and Locations

Study Contact

Murielle Hogu
CONTACT
(240) 858-3335
murielle.hogu@nih.gov
Udo Rudloff, M.D.
CONTACT
(240) 760-6238
rudloffu@mail.nih.gov

Principal Investigator

Udo Rudloff, M.D.
PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)

Study Locations (Sites)

University of Kansas
Fairway, Kansas, 66205
United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Udo Rudloff, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-10-27
Study Completion Date2028-12-31

Study Record Updates

Study Start Date2020-10-27
Study Completion Date2028-12-31

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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