A Phase 1, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of Intravenous Dimethane Sulfonate (DMS612, NSC 281612) in Advanced Malignancies
- The dimethane sulfonates are a group of agents that were identified as active against
renal cell carcinoma in the NCI anticancer drug screen.
- In vitro studies showed that dimethane sulfonates have properties in common with
alkylating agents, but are unlike conventional alkylators (such as nitrogen mustards,
BCNU, or busulfan) in that they are active against renal cell carcinoma (RCC).
-To determine dose-limiting toxicity (DLT), MTD and recommended phase II dose (RPTD) of
dimethane sulfonate (DMS612, NSC 281612) when administered by intravenous (IV) bolus on days
1 and 2 of a 21-day cycle.
- To evaluate non-dose limiting toxicities of DMS612
- To determine the pharmacokinetics of IV DMS612, NSC 281612 and its metabolites in
- To make a preliminary assessment of antitumor effect of IV DMS612, NSC 281612
- To correlate dose and pharmacokinetics with molecular measures of DMS612, NSC281612
- Patients must have histologically confirmed solid tumor malignancy or lymphoma that is
metastatic or unresectable and for which standard curative or palliative measures do
not exist or are no longer effective.
- Any prior chemotherapy therapy is allowed in this protocol.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are
currently available on the use of Dimethane sulfonate in patients less than 18 years of
age, children are excluded from this study but will be eligible for future pediatric
phase 1 single-agent trials.
- ECOG performance status 0-2 (Karnofsky greater than or equal to 60%,).
- Life expectancy of 3 months or greater.
- Patients must have acceptable organ and marrow function as defined below: leukocytes
greater than or equal to 3,000/mcL, absolute neutrophil count greater than or equal to
1,500/mm(3), platelets greater than or equal to 100,000/, mm(3) total bilirubin within
normal institutional limits, AST(SGOT)/ALT(SGPT), less than or equal to 2.5 times the
institutional upper limit of normal, creatinine within normal institutional limits or
creatinine clearance> 50mL/min for patients with creatinine levels above institutional
This is a Phase I study of the safety, pharmacokinetics, pharmacodynamics and antitumor
activity of IV DMS612, NSC 281612, designed as an open-label, dose-escalation study to
determine the RPTD of DMS612, NSC 281612 based on safety and pharmacokinetics.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting toxicity and maximum tolerated dose of DMS612.
Susan E Bates, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|Hershey Medical Center||Hershey, Pennsylvania 17033|