LMP744 (an indenoisoquinolone) for people with recurrent glioblastoma
Phase 1/Phase 2 Open Label Trial of a Novel Indenoisoquinolone C-MYC/TOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma
This trial will test whether the drug LMP744 can shrink tumors or slow progression in adults whose glioblastoma has returned after prior treatment.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 18 Years to 99 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT07416188 on ClinicalTrials.gov |
What this trial studies
Adults with histologically confirmed recurrent IDH‑wildtype glioblastoma undergo a baseline biopsy, receive an initial 5‑day infusion course of LMP744 (190 mg/m²/day over 1 hour), then have a second surgical biopsy or resection within 7 days to compare pre‑ and post‑treatment tissue. Tissue, cerebrospinal fluid, and blood will be analyzed for pharmacodynamic and molecular changes, and patients who recover will continue on repeated cycles of LMP744 (5 days on, 23 days off) for up to 12 cycles. A central venous port is placed for drug delivery and blood draws, and cardiac imaging and other safety monitoring are performed during participation. The primary clinical goal is to measure objective response rate, with progression‑free survival and other outcomes as secondary endpoints.
Who should consider this trial
Good fit: Adults (≥18 years) with pathologically confirmed recurrent IDH‑wildtype glioblastoma, Karnofsky Performance Status >60, who are willing to undergo brain biopsy or resection and have a central line placed are the intended candidates.
Not a fit: Patients with IDH‑mutant tumors, poor performance status (KPS ≤60), or those unable to tolerate or undergo biopsy/surgery and central line placement are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If LMP744 is effective, it could shrink tumors or delay progression and offer a new systemic option for patients with recurrent glioblastoma.
How similar studies have performed: Topoisomerase I inhibitors have shown limited clinical benefit in glioblastoma historically, and indenoisoquinolones like LMP744 are a newer class with promising preclinical data but limited prior clinical experience in brain tumors.
Eligibility criteria
Show full inclusion / exclusion criteria
* INCLUSION CRITERIA: Participant must meet all the following inclusion criteria to be deemed eligible for this study: * Participants \>= 18 years of age * Tissue-based diagnosis of recurrent glioblastoma, IDH-wildtype by a neuropathologist * Karnofsky Performance Status (KPS) \>60 * Willing to use effective birth control method --The effects of LMP744 on developing human fetuses are unknown. Therefore, females of childbearing potential and their male partners must be willing to use an effective method of contraception during the clinical study (hormonal, barrier, surgical, or abstinence) before study enrollment and for 6 months after the last dose of the study drug. If the female becomes pregnant or suspects she is pregnant while participating in this study, she must inform her treating physician immediately. * Agreeable to undergo craniotomy for brain biopsy and/or resection --Initial diagnostic biopsy under 03-N-0164 to confirm recurrent disease and obtain pre-treatment tissue. Only participants who were not expected to able to achieve a gross total resection of tumor will be included in the study. * Willing and able to appoint a durable power of attorney * Able to provide informed consent or have a legally authorized representative (LAR) to provide consent, if incapacitated. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Pregnant and/or nursing females --As LMP744 is a novel agent with the potential for teratogenic or abortifacient effects, pregnant and/or nursing females will be excluded from receiving drug * Significant medical co-morbidities that would compromise the participant s ability to tolerate LMP744 and which cannot reasonably be controlled (per the investigator s judgment, such as poorly controlled chronic kidney disease and/or poorly controlled congestive heart failure) * Social situations that would limit compliance with study requirements, such as chronic homelessness * Prior chemotherapy or biologic therapy completed within 4 weeks (6 weeks for nitrosoureas and mitomycin C) or a duration of 5 half-lives (whichever is shorter) * Additional malignancy diagnosed or requiring active treatment within 1 year of screening * Unable to undergo an MRI scan of the brain * Active autoimmune disease that requires systemic treatment within 2 years of screening * Cardiac disease * \>=2 MIs * \>=2 coronary revascularization procedures * Cardiac Troponin T or I \>= 2x the institutional upper limit of normal at screening * Ejection fraction \<45% on screening echocardiogram * Chronic hypokalemia (K\<2.5 mmol/L) * Human Immunodeficiency Virus (HIV) * Known history of HIV * Positive HIV 1/2 at screening. * Active Hepatitis B or Hepatitis C infection at screening * Active infection requiring systemic antibacterial, antiviral or antifungal therapy \<7 days prior to initiation of study drug * Recipient of autologous or allogeneic T cells * Solid organ or tissue transplant recipients
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Sadhana Jackson, M.D. — National Institute of Neurological Disorders and Stroke (NINDS)
- Study coordinator: Sadhana Jackson, M.D.
- Email: sadhana.jackson@nih.gov
- Phone: (301) 594-7037
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.