Ignite Creation Date:
2025-12-24 @ 9:10 PM
Ignite Modification Date:
2026-01-02 @ 8:59 AM
Study NCT ID:
NCT01794104
Status:
COMPLETED
Last Update Posted:
2018-09-27
First Post:
2013-02-15
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Indenoisoquinoline LMP400 for Advanced Solid Tumors and Lymphomas
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Trial of Weekly Indenoisoquinoline LMP400 in Adults With Relapsed Solid Tumors and Lymphomas
Status:
COMPLETED
Status Verified Date:
2017-10-27
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:
\- Indenoisoquinoline LMP400 is an experimental cancer treatment drug. It damages DNA in tumor cells. Tumor cells with damaged DNA may die, resulting in cell death. Researchers want to see if this drug is a safe and effective treatment for solid tumors and lymphomas that have not responded to earlier treatment.
Objectives:
\- To see if Indenoisoquinoline LMP400 is a safe and effective treatment for advanced solid tumors or lymphomas.
Eligibility:
\- Individuals at least 18 years of age who have solid tumors or lymphomas that have not responded to treatment.
Design:
* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies.
* Indenoisoquinoline LMP400 is given in a 28-day cycle. Participants will receive the drug by intravenous infusion on days 1, 8, and 15 of each cycle, followed by a break of 13 days without the drug.
* Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will be optional.
* Participants will continue their cycles of treatment as long as the cancer does not grow and there are no severe side effects.
\- Indenoisoquinoline LMP400 is an experimental cancer treatment drug. It damages DNA in tumor cells. Tumor cells with damaged DNA may die, resulting in cell death. Researchers want to see if this drug is a safe and effective treatment for solid tumors and lymphomas that have not responded to earlier treatment.
Objectives:
\- To see if Indenoisoquinoline LMP400 is a safe and effective treatment for advanced solid tumors or lymphomas.
Eligibility:
\- Individuals at least 18 years of age who have solid tumors or lymphomas that have not responded to treatment.
Design:
* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies.
* Indenoisoquinoline LMP400 is given in a 28-day cycle. Participants will receive the drug by intravenous infusion on days 1, 8, and 15 of each cycle, followed by a break of 13 days without the drug.
* Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will be optional.
* Participants will continue their cycles of treatment as long as the cancer does not grow and there are no severe side effects.
Detailed Description:
Background:
* Indenoisoquinolines are non-camptothecin topoisomerase (Top1) inhibitors that form stable DNA-Top1 cleavage-complexes, have a preference for unique DNA cleavage sites, and are active against camptothecin-resistant cell lines. Unlike camptothecins, indenoisoquinolines are chemically stable and active in cells that over-express ATP-binding cassette (ABC) transporters ABCG2 and multidrug resistance (MDR-1). Top1 inhibitors are potent anticancer agents because stabilizing cleavage complex formation induces replication-and transcription-mediated DNA damage and delays DNA repair, leading to apoptosis. Preclinical and clinical data indicate that baseline tumor levels of Top1 correlate strongly with ability to respond to Top1 inhibitor therapy.
* A first-in-human Phase I study conducted at the NCI of the indenoisoquinoline LMP400 (NSC 743400) on a QD x 5 q28 schedule in patients with refractory solid tumors and lymphomas (10-C-0056) established that this agent is well tolerated. LMP400 shows linear pharmacokinetics with evidence of drug accumulation following 5 days of dosing. We hypothesize that weekly dosing (days 1, 8, 15 q28-day cycle) will increase LMP400 peak levels and exposures, improving clinical activity and safety.
Primary Objectives:
* To establish the safety and tolerability of weekly (days 1, 8, 15 q28-day cycle) LMP400 in patients with refractory solid tumors and lymphomas.
* To establish the maximum tolerated dose (MTD) of weekly LMP400 in patients with refractory solid tumors and lymphomas.
* To evaluate the pharmacokinetic profile of weekly LMP400.
Secondary Objectives:
* Evaluate the level of Top1 in tumor biopsies pre- and post- administration of LMP400.
* Evaluate the effect of LMP400 on markers of DNA damage and apoptosis, such as \>=H2AX and caspase 3, in tumor biopsies pre- and post- LMP400 administration.
Eligibility:
-Patients with histologically confirmed metastatic solid tumors and lymphomas; adequate organ function.
Study Design:
* This is an open-label Phase I trial evaluating weekly administration of LMP400, on days 1, 8, and 15, in 28-day cycles.
* Starting dose is based on the MTD determined from the QD x 5, q28 day schedule currently being evaluated. The study will follow a 3 plus 3 design.
* Once the MTD is established, 10 additional patients will be enrolled at the MTD to further define the pharmacokinetics and evaluate effect of study drug on DNA damage and apoptosis.
* Indenoisoquinolines are non-camptothecin topoisomerase (Top1) inhibitors that form stable DNA-Top1 cleavage-complexes, have a preference for unique DNA cleavage sites, and are active against camptothecin-resistant cell lines. Unlike camptothecins, indenoisoquinolines are chemically stable and active in cells that over-express ATP-binding cassette (ABC) transporters ABCG2 and multidrug resistance (MDR-1). Top1 inhibitors are potent anticancer agents because stabilizing cleavage complex formation induces replication-and transcription-mediated DNA damage and delays DNA repair, leading to apoptosis. Preclinical and clinical data indicate that baseline tumor levels of Top1 correlate strongly with ability to respond to Top1 inhibitor therapy.
* A first-in-human Phase I study conducted at the NCI of the indenoisoquinoline LMP400 (NSC 743400) on a QD x 5 q28 schedule in patients with refractory solid tumors and lymphomas (10-C-0056) established that this agent is well tolerated. LMP400 shows linear pharmacokinetics with evidence of drug accumulation following 5 days of dosing. We hypothesize that weekly dosing (days 1, 8, 15 q28-day cycle) will increase LMP400 peak levels and exposures, improving clinical activity and safety.
Primary Objectives:
* To establish the safety and tolerability of weekly (days 1, 8, 15 q28-day cycle) LMP400 in patients with refractory solid tumors and lymphomas.
* To establish the maximum tolerated dose (MTD) of weekly LMP400 in patients with refractory solid tumors and lymphomas.
* To evaluate the pharmacokinetic profile of weekly LMP400.
Secondary Objectives:
* Evaluate the level of Top1 in tumor biopsies pre- and post- administration of LMP400.
* Evaluate the effect of LMP400 on markers of DNA damage and apoptosis, such as \>=H2AX and caspase 3, in tumor biopsies pre- and post- LMP400 administration.
Eligibility:
-Patients with histologically confirmed metastatic solid tumors and lymphomas; adequate organ function.
Study Design:
* This is an open-label Phase I trial evaluating weekly administration of LMP400, on days 1, 8, and 15, in 28-day cycles.
* Starting dose is based on the MTD determined from the QD x 5, q28 day schedule currently being evaluated. The study will follow a 3 plus 3 design.
* Once the MTD is established, 10 additional patients will be enrolled at the MTD to further define the pharmacokinetics and evaluate effect of study drug on DNA damage and apoptosis.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 13-C-0080 | None | None | View |