Ignite Creation Date:
2025-12-25 @ 4:17 AM
Ignite Modification Date:
2025-12-26 @ 3:17 AM
Study NCT ID:
NCT00923520
Status:
COMPLETED
Last Update Posted:
2018-12-05
First Post:
2009-06-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Phase 1, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Dimethane Sulfonate (DMS612) in Advanced Malignancies
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 1, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of Intravenous Dimethane Sulfonate (DMS612, NSC 281612) in Advanced Malignancies
Status:
COMPLETED
Status Verified Date:
2018-12-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
* 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 --
* 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 --
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 09-C-0111 | None | None | View |