Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas
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|ClinicalTrials.gov Identifier: NCT03030417|
Recruitment Status : Recruiting
First Posted : January 25, 2017
Last Update Posted : July 23, 2021
The new drug LMP744 damages DNA. This causes cell death. Researchers want to see if it can treat certain kinds of cancer. They want to understand how the drug works and how it affects the body.
To test the safety of LMP744 and find out the dose of the drug that can be safely given to humans.
Adults at least 18 years old who have metastatic solid tumors or lymphoma, which have progressed after other treatment.
Participants will be screened with:
- Vital signs taken
- Blood and urine tests
- Heart tests
- Scans or ultrasound
Some participants will have a tumor sample taken 2 times. A small piece of tumor is removed by a small needle. A scan or ultrasound will guide the process.
The study will be done in 28-day cycles.
Each cycle, participants will get the study drug in a vein for 60 minutes once a day for 5 days.
For day 1 of cycle 1, participants will be admitted to the clinic and have blood and urine taken several times.
At the beginning of each cycle, participants will have a clinic visit and repeat some screening tests. They will also do this twice in the middle of cycle 1 and once in the middle of cycle 2.
After participants stop taking the study drug, they will be followed for 30 days. They may give blood samples. They will be contacted by phone to see how they are doing.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors Lymphoma||Drug: LMP744||Phase 1|
- Indenoisoquinolines are non-camptothecin inhibitors of topoisomerase 1 (top1) withimproved characteristics over their predecessors. Indenoisoquinolines have better chemical stability, producing stable DNA-top1 cleavage complexes, and exhibit a preference for unique DNA cleavage sites, compared with their camptothecin counterparts.
- They have demonstrated activity against camptothecin-resistant cell lines and produce DNA-protein crosslinks, which are resistant to reversal. They also show less or no resistance to cells overexpressing the ATP-binding cassette (ABC) transporters, ABCG2, and multidrug resistance (MDR-1).
-To establish the safety, tolerability and the maximum tolerated dose (MTD) of LMP744 (NSC 706744) administered intravenously (IV) daily for 5 days (QD x 5) schedule in patients with refractory solid tumors and lymphomas.
-Characterize the pharmacokinetic (PK) profile of LMP744.
- Evaluate the effect of LMP744 on markers of DNA damage ( >=H2AX, pNbs1, pATR, ERCC1, RAD51) and epithelial-mesenchymal transition (EMT) in circulating tumor cells (CTCs) and pre- and post- treatment tumor biopsies in patients at the expansion cohort.
- Assess preliminary antitumor activity of LMP744.
-Adult patients must have histologically documented, relapsed solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after initial therapy and without potentially curative options, or patient refuses potentially curative therapy.
- Cycle 1 and subsequent cycles: Patients will receive LMP744 administered IV QD over 1 hour on days 1 5 followed by 23 days without drug (28-day cycle).
- PK and PD samples will be collected. Tumor biopsies will be optional during the escalation phase and mandatory during the expansion phase.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas|
|Actual Study Start Date :||February 27, 2017|
|Estimated Primary Completion Date :||October 2, 2022|
|Estimated Study Completion Date :||October 2, 2022|
Experimental: Treatment Arm
LMP744 will be administered IV over 1 hour on days 1-5 of each 28-day cycle
Indenoisoquinolines, such as LMP744, are potent inhibitors of the enzyme topoisomerase I (Top1). Top1 is necessary for transcription, replication, recombination, and the repair of double-strand DNA breaks. It relaxes the supercoiled DNA by introducing a single-strand break, generating a free strand that rotates around the Top1-bound DNA complex. In the absence of external triggers, Top1-DNA cleavage complexes are generally short lived. Top1 inhibitors are potent anticancer agents because they stabilize the formation of the Top1- DNA cleavage complex in tumor cells, which induces DNA damage, delays DNA repair, and results in cell cycle arrest and apoptosis. LMP744 exhibited antitumor activity with lower toxicity than other agents in preclinical studies. Treatment of patients with LMP744 is expected to reduce tumor burden at doses that are well-tolerated.
- To establish the safety, tolerability and the maximum tolerated dose(MTD) of LMP744 (NSC 706744) [ Time Frame: cycle 1 ]Maximum tolerated dose (MTD) of LMP744 administered intravenously (IV) daily for 5 days (QD x 5) schedule in patients with refractory solid tumors and lymphomas
- Characterize the pharmacokinetic (PK) profile of LMP744 [ Time Frame: cycle 1 ]Characterize the pharmacokinetic (PK) profile of LMP744
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030417
|Contact: Brooksley F Augustine||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|United States, Pennsylvania|
|University of Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15260|
|Contact: Anuradha Krishnamurthy, M.D. 412-864-7764 email@example.com|
|Principal Investigator:||Geraldine H O'Sullivan Coyne, M.D.||National Cancer Institute (NCI)|