RecruitingPhase 1

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
12 Years to 120 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Questionnaires, MRI scans, CT scans, X-rays, Biopsies, Phone or video check-ins

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "They will fill out questionnaires."
  • "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."
  • "Then they will have follow-up phone calls or emails every 6 months for the rest of their life or until the study ends."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests a drug called metarrestin to find a safe dose and see if it shrinks tumors. It is for adults and some children ages 12–17 whose solid cancer has spread or returned, and whose standard treatment has failed or is not available.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Adults must have a solid tumor confirmed by tissue or cell tests. Some study groups accept only pancreatic, colon, rectal, or breast cancer.
  • Children ages 12–17 must have a confirmed solid tumor other than rhabdomyosarcoma, a type of muscle cancer.
  • Cancer must have spread to another organ or returned after surgery, and surgery must not offer a possible cure. Some groups require tumors that can be measured on scans.
  • Cancer must have worsened during or after standard chemotherapy, or there must be no standard treatment option, depending on the study group.
  • You must have recovered from major effects of past treatment, surgery, or disease and be able to do most daily activities. Blood counts, blood clotting, liver, and kidney tests must meet study limits.
  • Adults must weigh at least 35 kg (about 77 pounds); children must weigh at least 40 kg (about 88 pounds). You must be able to swallow capsules.
  • If you could become pregnant or father a child, you must use birth control before treatment, during treatment, and for 120 days afterward. You must stop breastfeeding when treatment starts.
  • You or your parent or guardian must agree in writing to join. One study group requires a tumor that can be sampled and agreement to have biopsies, which remove small tissue samples.

Who can't join

  • You had cancer treatment or surgery too recently. Waiting times depend on the treatment, usually 14–28 days. You also cannot join if you cannot safely stop certain medicines that affect how the body handles the study drug.
  • You have certain heart muscle, heart valve, heart pumping, or heart rhythm problems.
  • You have HIV or hepatitis B or C and take antiviral drugs, or you have a serious infection with symptoms.
  • You had another cancer within the past 3 years, except certain early cancers treated with the goal of a cure.
  • Cancer has spread to your brain or spinal cord, or you have certain nervous system conditions, such as a recent stroke. A history of seizures or a brain-wave test showing seizure risk also rules you out.
  • Your cancer is worsening too quickly, or another illness could make treatment or study visits unsafe or too hard.
  • You had gastric bypass surgery, get nutrition through a feeding tube or vein, have trouble absorbing food, or have nausea and vomiting that do not improve with treatment.
  • You are pregnant.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

* 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 organ system other than primary tumor or recurred after removal of primary tumor * has site measurable per RECIST 1.1 (Phase IB only). * 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, * transfusion-independent platelet count \>= 100 x 10(9)/L, * Hgb \>= 9 g/ dL (patients who have received \<= 2 PRBC transfusions within 48 hours are eligible) * Adequate coagulation as defined by: --INR\<1.5 (or \< 3.0 if subjects are currently taking anticoagulated medications) Note: increase of the upper limit of INR is restricted only to subjects who are receiving anticoagulation for medical reasons (DVT/PE prophylaxis, treatment for a thromboembolic event) and have increased INR because of these medications. Patients who have an elevated INR due to compromised liver function or any other medical conditions remain excluded * Adequate hepatic function defined by: --a total bilirubin level \<= 1.5 x ULN, (total bilirubin \<= 2.0 x ULN in case of prior diagnosis of Gilbert syndrome) * an AST level \<= 3xULN * an ALT level \<= 3 xULN * Adequate renal function defined by: --Creatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl)\* ---\< 1.5x institution upper limit of normal OR ---\>= 45 mL/min/1.73 m\^2 for participant with creatinine levels \>= 1.5 X institutional ULN \*Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard. * 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 to study entry, for the duration of study therapy and up to 120 days after the last dose of the study drug. * Nursing participants must be willing to discontinue nursing at the time of the study treatment initiation. * Weight: \>= 35 kg (\>= 18 years old) or \>=40 kg (\>= 12 and \< 18 years old). * Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document. * 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). * Ability to swallow oral capsules. EXCLUSION CRITERIA: * 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 * atrial fibrillation with a ventricular rate \>100 bpm on EKG at rest * 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. * 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. * 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. * Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures. * 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). * Significant acute or chronic infections including tuberculosis with presence of clinical symptoms or physical findings. * 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. * 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. * 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. * Pregnant individuals.

Study sites (2)

KS

MD

  • National Institutes of Health Clinical Center · Bethesda, MD 20892For more information at the NIH Clinical Center contact National Cancer Institute Referral Office · Study contact · 888-624-1937More trials in Bethesda