A Phase 1, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Dimethane Sulfonate (DMS612) in Advanced Malignancies
Condition: Renal Cell Carcinoma; Breast Cancer; Colon Cancer; Lung Cancer; Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Colonic Neoplasms; Carcinoma, Renal Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Dimethane sulfonate (DMS612) is an investigational drug that is being administered to
           humans for the first time in people with advanced tumors. More information on the
           maximum tolerated dose of DMS612 will help researchers identify whether the drug is
           suitable for use in treating certain kinds of cancer, particularly renal cell carcinoma.

      Objectives:

        -  To determine the maximum tolerated dose of DMS612 (the highest dose that does not cause
           unacceptable side effects) and evaluate any side effects.

        -  To see if DMS612 has any effect on patients tumors through blood tests and laboratory
           studies.

        -  To learn how the body processes DMS612.

      Eligibility:

        -  Patients 18 years of age and older who have been diagnosed with cancer that has not
           responded well to standard treatments.

      Design:

        -  Pre-treatment evaluation visit to determine eligibility:

        -  Physical examination

        -  Blood and urine tests

        -  Chest X-ray; electrocardiogram; CAT scan of chest, abdomen, pelvis, and other areas of
           the body if needed

        -  Other possible tests, such as magnetic resonance imaging (MRI) or positron emission
           tomography (PET)

        -  Patients will receive one dose of DMS612 by intravenous infusion once a week for 3
           weeks, followed by 1 week without the drug. Doses will be adjusted based on possible
           side effects and cancer response. The disease will be evaluated after three cycles of
           the drug.

        -  Evaluations during the treatment period:

        -  Physical examination and reviews of side effects.

        -  Blood draws to evaluate the effectiveness of the drug, and how it is processed by the
           body.

        -  CAT scan at the end of every two cycles (every 8 weeks).

        -  Other scans and imaging procedures as required by the study doctors.
    

Detailed description: 
      Background:

        -  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).

      Objective:

      Primary:

      -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 day 1
      and 2 of a 21-day cycle.

      Eligibility:

        -  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. No more than 2 prior
           cytotoxic chemotherapy regimens are allowed.

        -  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 greater than 50mL/min for patients with creatinine levels above
           institutional normal.

      Design:

      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. With the
      02/09/2015 amendment and change in schedule to evaluate a day 1 and 2 dosing every 6 weeks
      the following schema will be used:

      Dose Level Dose of NSC 281612 Escalation (%)

        -  1 3.5 mg/m2 on Day 1 and 2 -33

           4A 4.5 mg/m2 on Day 1 and 2 ---

           5A 6 mg/m2 on Day 1 and 2 33

           6A 8 mg/m2 on Day 1 and 2 67

           7A 10.5 mg/m2 on Day 1 and 2 33

           7B 10.5 mg/m2 on Day 1 and 2 q 6 weeks ---

           8A 14 mg/m2 on Day 1 and 2 33

           8B 14 mg/m2 on Day 1 and 2 q 6 weeks --
    

Intervention name(s): DMS 612
Intervention type(s): Drug
Intervention description(s): DMS 612 on day 1 and 2 with doses starting at 3.5mg/m2 to 18.5mg/m2 every 21 days until MTD is reached
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Solid Tumors; Phase I; Lymphoma; Dimethane Sulfonate (DMS612, NSC 281612); Cancer; Solid Tumor; Renal Cell Cancer; Kidney Cancer; Breast Cancer; Colon Cancer; Lung Disease; Non-Hodgkin Lymphoma; NHL