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View Clinical Trial (Medical Research Study)
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A Phase 1, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Dimethane Sulfonate (DMS612) in Advanced Malignancies - NCT00923520-17033 (Clinical Trial 298463)
Permalink: http://www.ClinicalConnection.com/exp/ExpandedPatientViewStudy298463.aspx
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| City: |
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Hershey |
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State:
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PA |
| Zip Code: |
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17033 |
| Conditions: |
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Renal Cell Carcinoma - Breast Cancer - Colon Cancer - Lung Cancer - Non-Hodgkin Lymphoma |
| Purpose: |
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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.
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| Study summary: |
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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 days
1, 8 and 15 of a 28-day cycle.
Secondary:
- To evaluate non-dose limiting toxicities of DMS612
- To determine the pharmacokinetics of IV DMS612, NSC 281612 and its metabolites in
humans.
- To make a preliminary assessment of antitumor effect of IV DMS612, NSC 281612
- To correlate dose and pharmacokinetics with molecular measures of BDMS612, NSC 281612
effect.
- To evaluate potential correlations between aldehyde dehydrogenase genotype and the
pharmacokinetics and pharmacodynamics of NSC 281612.
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.
- 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 < 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
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. A 1.5 mg/m(2)
dose level will be the starting dose level of DMS612, NSC 281612. |
| Criteria: |
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- INCLUSION CRITERIA:
- Patients must have histologically confirmed solid tumor malignancy or lymphoma that
is metastatic or unresectable and for which effective therapy does not exist or is no
longer effective.
- Any prior chemotherapy therapy is allowed in this protocol. Patients must be greater
than or equal to 4 weeks from prior radiation or cytotoxic chemotherapy, except
greater than or equal to 6 weeks for mitomycin C and nitrosoureas; greater than or
equal to 2 weeks from hormonal therapy; greater than or equal to 4 weeks from prior
experimental therapy; greater than or equal to 4 weeks from monoclonal antibody
therapy (cetuximab, bevacizumab), greater than or equal to 2 weeks from sorafenib,
sunitinib or temsirolimus and greater than or equal to 8 weeks from prior UCN01
treatment. Patients with prostate cancer may continue ongoing LHRH agonist therapy.
Patients with bone metastases or hypercalcemia who began intravenous bisphosphonate
treatment prior to study entry may continue this treatment.
- 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 < 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/mm(3)
- 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 X institutional upper limit of
normal
- creatinine within normal institutional limits OR
- creatinine clearance > 50 mL/min/1.73 m(2) for patients with creatinine levels
above institutional normal.
- The effects of dimethane sulfonate on the developing human fetus are unknown. For
this reason and because alkylating agents are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for at least 3
months after study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately.
- Ability to understand and the willingness to sign a written informed consent
document.
- Willing to comply with study procedures and follow-up.
EXCLUSION CRITERIA:
- Patients who have not recovered (CTC less than or equal to grade I) from adverse
events due to prior treatments
- Patients may not be receiving any other investigational agent with therapeutic
anticancer intent.
- Patients with history of CNS metastasis, unless control has been achieved with either
radiation or surgical resection at least 6 months prior to enrollment on study.
- Patients who have had radiation to the pelvis or other bone marrow-bearing sites will
be considered on a case by case basis and may be excluded if the bone marrow reserve
is not considered adequate (> 25% of bone marrow irradiated).
- Uncontrolled medical illness including, but not limited to, ongoing or active
infection, chronic or acute hepatitis, renal failure, symptomatic congestive heart
failure, myocardial infarction within the last 6 months, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.
- Pregnant women are excluded from this study because DMS612 is likely to have
toxicities similar to the alklyating agents with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with DMS612,
breastfeeding should be discontinued if the mother is treated with DMS612.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with DMS612. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.
- Patients are not eligible for the study if taking cytochrome P450-inducing
anticonvulsants. This applies to patients with brain metastasis or those taking
anticonvulsant for another reason (ie. Epilepsy).
- Patients diagnosed with alcoholism may not be treated with disulfiram.
- Patients may not be receiving agents thought to inhibit or induce the cytochrome p450
isoenzyme CYP3A4. |
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| Study is available at: |
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Hershey Medical Center
Hershey, PA 17033
United States
Primary Contact:
NCI Referral Office
Email: ncicssc@mail.nih.gov
Phone: 1-888-NCI-1937 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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November 16, 2009 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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Clinical trials are medical research studies designed to test the safety and/or
effectiveness of new drugs, devices, or treatments in humans. These studies are
conducted worldwide for a range of conditions and illnesses. Learn more about
clinical research and participating in a study at
About Clinical Trials.
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