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.
histologically or cytologically confirmed solid tumors (Phase IA).
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).
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
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;
Sequential
Metarrestin
DrugPhase 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
To identify the maximum tolerated dose (MTD) of metarrestin in subjects with metastatic solid tumors
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
Fraction of objective responses determined and reported as the ORR
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
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 determine plasma PK levels of metarrestin in humans
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 assess progression-free survival (PFS) according to RECIST 1.1
Median amount of time subject survives without disease progression after treatment
To determine duration of overall response (DOR) rate according to Response Evaluation Criteria (RECIST 1.1) in subjects with metastatic solid tumors
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
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