15 Participants Needed

Alrizomadlin for Mesothelioma

DF
DS
DC
Overseen ByDeneise C Francis, R.N.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain medications like CYP3A4/3A5 inhibitors or inducers, P-glycoprotein inhibitors, or therapeutic anticoagulants within two weeks before starting the trial.

What makes the drug Alrizomadlin unique for treating mesothelioma?

Alrizomadlin (APG-115) is a novel drug being tested for mesothelioma, which is a condition with limited effective treatments. Unlike traditional chemotherapy, Alrizomadlin may work by targeting specific pathways involved in cancer cell survival, offering a new approach to treatment.12345

What is the purpose of this trial?

Background:Mesothelioma is a rare cancer typically caused by exposure to asbestos and related fibers. Most people with mesothelioma survive less than 5 years after diagnosis. About 3000 people in the United States die from this disease each year. People with inherited mutations in the BAP1 gene \[called BAP1 Cancer Syndrome (BCS)\] are more likely to develop mesothelioma and other cancers such as melanomas and renal cell carcinomas without asbestos exposure. Almost all people with BCS develop multiple cancers, of which mesothelioma is the most commonly observed.Objective:To test a study drug (APG-115) in participants with BAP1 Cancer Syndrome (BCS) and early-stage mesothelioma.Eligibility:People aged 18 years and older with germline BAP1 mutations and early-stage mesothelioma that does not yet need standard treatment are eligible for protocol enrollment. Participants will be required to also enroll in NIH protocols 20-C-0106 and 06-C-0014 which allow for pre- and post-treatment biopsies and bloodwork to be obtained for additional research studies.Design:Participants will be screened. They will have a physical exam with blood tests. Their medical records will be reviewed. They will have imaging scans and tests of their heart and lung functions. A procedure using a flexible tube with a camera and light will be inserted into the participant s chest and abdomen through a small cut to look at the tumors and to collect a tissue sample (biopsy).APG-115 capsules are taken by mouth. Participants will take the drug at home every other day for the first 13 days of the 21-day treatment cycles.On the first day of each cycle, researchers will call or email participants to check on their health.Participants will have blood tests 2 times a week during the first 2 cycles; after that, the blood tests will be weekly. These blood tests can be done at a local medical facility or at the NIH Clinical Center.Participants may continue treatment for up to 16 cycles.Imaging scans, biopsy, and other tests will be repeated after 8 and 16 cycles.

Research Team

DS

David S Schrump, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for individuals with early-stage mesothelioma, a type of cancer that affects the lining of the lungs, and who have BAP1 Cancer Syndrome. Participants should carry specific genetic changes known as BAP1 mutations.

Inclusion Criteria

Nursing participants must discontinue nursing during the study
Willingness to co-enroll on other specified studies for data collection
Agreement to use effective contraception
See 10 more

Exclusion Criteria

QTcF interval > 470 ms
Positive Hepatitis A, B, or C serological test
Seropositive for human immunodeficiency virus (HIV) infection
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive APG-115 orally every other day for the first 13 days of a 21-day cycle, up to 16 cycles

48 weeks
Blood tests 2 times a week during the first 2 cycles, then weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
1 visit (in-person) for safety assessment

Extension

Participants with stable disease or disease regression may continue treatment for an additional 8 cycles

24 weeks

Treatment Details

Interventions

  • Alrizomadlin (APG-115)
Trial Overview The study is testing alrizomadlin (APG-115) to see if it can stabilize or improve mesothelioma in patients with BAP1 Cancer Syndrome. It's a phase II trial, which means they're looking at how well the drug works and checking its safety.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: 1/ Arm 1Experimental Treatment1 Intervention
APG-115

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Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

The MESOMARK assay for measuring soluble mesothelin-related peptides (SMRP) is a reliable and robust tool, showing high precision and stability, making it suitable for clinical use in detecting malignant pleural mesothelioma (MPM).
In a study of 500 cancer patients, including 88 with MPM, the assay revealed significantly elevated SMRP levels in MPM patients (7.5 nmol/L) compared to healthy individuals (1.5 nmol/L), indicating its potential as a biomarker for this type of cancer.
MESOMARK: a potential test for malignant pleural mesothelioma.Beyer, HL., Geschwindt, RD., Glover, CL., et al.[2022]
A screening of 1170 FDA-approved drugs identified cephalomannine, ouabain, thonzonium bromide, and emetine as highly effective against malignant pleural mesothelioma (MPM) cell lines, showing significant cytotoxicity and inhibition of cell proliferation.
These drugs, except for alexidine, demonstrated the ability to activate caspases and inhibit clonogenic ability across multiple MPM cell lines, suggesting they could be promising candidates for repurposing in MPM treatment.
A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma.Dell'Anno, I., Melani, A., Martin, SA., et al.[2023]
Malignant mesothelioma is a challenging cancer primarily caused by environmental factors like asbestos, and most patients are not suitable for surgery or radiation, leaving cytotoxic agents as the main treatment option.
Recent trials have shown that pemetrexed, when combined with cisplatin, can achieve a response rate of 14.1% and a 1-year survival rate of 47.8%, indicating potential efficacy in treating this aggressive cancer.
Emerging insights into the biology and therapy of malignant mesothelioma.Vogelzang, NJ.[2022]

References

Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma. [2022]
MESOMARK: a potential test for malignant pleural mesothelioma. [2022]
Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma. [2021]
A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma. [2023]
Emerging insights into the biology and therapy of malignant mesothelioma. [2022]
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