Health TrialsbyHealthPanel

Novel Indenoisoquinolone CMYC/TOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma

ConditionsRecurrent GlioblastomaGlioblastoma IDH (Isocitrate Dehydrogenase) WildtypeRelapsed CancerRecurrent TumorGlioblastoma MultiformeRecurring GlioblastomaBrain and Central Nervous System TumorsGliomaGlioblastomasGrade IV AstrocytomaGBMRecurrent Glioma (Glioblastoma Multiforme)High Grade GliomaGlioma, MalignantBrain Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-99
SponsorNational Institute of Neurological Disorders and Stroke (NINDS)

About this trial

Background:

Glioblastoma is a common brain cancer in adults. Treatment includes surgery, radiation, and chemotherapy. But this cancer can return after treatment and is often fatal. Researchers want to know if a study drug (LMP744) can kill glioblastoma tumor cells.

Objective:

To test LMP744 in people with glioblastoma.

Eligibility:

People aged 18 years or older with glioblastoma that returned after treatment.

Design:

Participants will be screened. They will have a surgery to remove a small sample of tumor tissue (biopsy) from the brain. This will be done under protocol 03-N-0164. They will stay in the clinic for 1 night. They will also have imaging scans and tests of their heart function.

Participants will have a central line installed: A flexible tube will be inserted into a vein in the chest. It will be attached to a "port" under the skin. This port will be used to draw blood and give medicines without having to insert new needles into a vein.

LMP744 will be given through the central line for 5 days in a row. Participants will remain in the clinic for this time.

Participants will then have a second surgery to remove as much of their tumor as possible. They will remain in the clinic until they recover from the surgery. Then they will recover at home after surgery.

Participants will return to the clinic to receive the study drug for 5 days in a row through the central line, once a month for up to 12 months. Blood tests, heart function tests, and periodic imaging scans will be repeated during these visits.

Participants will continue to have telehealth visits every 3 months after they stop taking the drug.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Pregnant and/or nursing females

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)

Trial design

Design model

Single group

Treatments tested in this trial

  • LMP744

    Drug

    Indenoisoquinolone C-MYC/TOPOISOMERASE 1 Inhibitor

  • Conventional Surgery or Biopsy

    Procedure/Surgery

    Conventional Surgery or Biopsy

Treatment groups

40 Participants
are divided into 1 treatment group
Group A: Arm AExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Partial response (>=50% disease reduction) or complete response (100% disease reduction) based on RANO 2.0 criteria

As ORR is associated with survival experience, this endpoint allows for objective evaluation of efficacy of LMP744 in this proof-of-concept phase 2 trial

Time frame
5 years

Secondary outcomes

1

Progression-Free Survival (PFS): Time from the start of treatment with LMP744 until disease progression based on RANO 2.0 criteria

PFS provides a measure of treatment efficacy in delaying tumor progression. While the study is not powered to demonstrate superiority of LMP744 to concurrent controls, the study will compare LMP744 to historical controls to generate information for planning of a future phase 3 trial.

Time frame
5 years
2

Overall Survival (OS): Time from the start of treatment with LMP744 until death from any cause

OS is the gold standard for assessing the ultimate benefit of a therapy on survival. We will compare OS between LMP744 and historical controls to provide information for planning of a future phase 3 trial

Time frame
5 years
3

Changes in transcriptomic and proteomic profiles before and after LMP744 treatment

Evaluating changes in these markers will provide insight into the pharmacodynamic effects of LMP744 at the molecular level. The selected markers are involved in DNA damage response, cell cycle regulation, and survival pathways, which are critical in understanding the tumor's response to the drug.

Time frame
5 years
4

Change in self-reported quality of life (QOL) as measured by the SF-36 survey at baseline, after each treatment cycle, and at study completion.

The SF-36 is a validated tool for assessing the quality of life in cancer patients and captures the broad impact of treatment on physical, emotional, and social well-being. Tracking changes in QOL over time will provide insight into the patient-reported outcomes related to LMP744 treatment. This endpoint is essential for understanding the broader implications of treatment beyond clinical and molecular measures, giving a more comprehensive assessment of treatment benefit or burden.

Time frame
5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Institute of Neurological Disorders and Stroke (NINDS)

Lead sponsor

Source ClinicalTrials.gov
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