Brentuximab Vedotin for Inoperable Mesothelioma

Overseen By Anne S. Tsao

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Psychiatric illness, Recent malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

55 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is the drug Brentuximab Vedotin unique for treating inoperable mesothelioma?

Brentuximab Vedotin is unique because it targets the CD30 antigen, which is present in some mesothelioma tumors, and has shown success in reducing cell growth in these cases. This approach is different from standard chemotherapy, as it specifically targets a protein found on the surface of certain cancer cells. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial studies how well brentuximab vedotin works in treating patients with CD30 positive (+) malignant mesothelioma that cannot be removed by surgery. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of tumor cells to grow and spread.

Research Team

Anne S. Tsao

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for male and female patients with CD30+ malignant mesothelioma that can't be surgically removed. Participants need to agree to contraception, have had any prior treatments, and their major organs must function well. Exclusions include a recent history of other cancers, significant bone marrow radiation, organ transplants, current participation in other studies, serious health or mental issues, pregnancy or breastfeeding.

Inclusion Criteria

Your total bilirubin level is not higher than 1.5 times the upper limit of normal.

I agree to use or have used a reliable form of birth control or abstain from sex for the study duration and 6 months after.

I am a woman who is post-menopausal, surgically sterilized, or will use birth control during and 6 months after the study.

Exclusion Criteria

I am not pregnant or breastfeeding, confirmed by a negative pregnancy test.

Patient has received other investigational drugs with 14 days before enrollment

You are allergic to any parts of brentuximab vedotin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin intravenously over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 30 days, 3 months, 6 months, and then every 6 months thereafter.

Up to 5 years

Treatment Details

Interventions

• Brentuximab Vedotin

Trial Overview The study tests Brentuximab Vedotin's effectiveness on patients with inoperable CD30+ malignant mesothelioma. It's a phase II trial where this monoclonal antibody is used to see if it can stop cancer cells from growing and spreading.

Participant Groups

Group I: Treatment (brentuximab vedotin) Experimental Treatment 2 Interventions

Patients receive brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma. Dell'Anno, I., Melani, A., Martin, SA., et al.[2023]

BRCA1 expression levels are strongly correlated with sensitivity to the chemotherapy drug vinorelbine in malignant pleural mesothelioma, indicating that BRCA1 may be a key factor in determining treatment effectiveness.

In a study of 144 mesothelioma samples, 38.9% showed loss of BRCA1 protein expression, suggesting that assessing BRCA1 levels could help predict patient responses to vinorelbine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma. Busacca, S., Sheaff, M., Arthur, K., et al.[2018]

In a study of 83 mesothelioma tumor specimens, CD30 expression was found in 13 cases, primarily in epithelial-type tumors, suggesting a potential target for treatment.

Brentuximab vedotin, an antibody-drug conjugate targeting CD30, demonstrated a dose-dependent reduction in cell growth and viability in mesothelioma cell lines, indicating that some patients with mesothelioma may benefit from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD30 is a potential therapeutic target in malignant mesothelioma. Dabir, S., Kresak, A., Yang, M., et al.[2020]

Mesothelin is a promising target for cancer immunotherapy due to its high expression in various cancers and limited normal expression, making it a safer option for treatment.

Several antibody-based therapies and T-cell therapies targeting mesothelin are currently in clinical trials, including amatuximab and anetumab ravtansine for malignant mesothelioma, which could lead to new treatment options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesothelin Immunotherapy for Cancer: Ready for Prime Time? Hassan, R., Thomas, A., Alewine, C., et al.[2022]

The standard treatment for malignant mesothelioma, which is a challenging cancer to treat, has recently been established as a combination of pemetrexed and cisplatin, but the prognosis remains poor with a median survival of less than two years.

Research is ongoing into targeted therapies, including agents that inhibit growth factor signaling and the ubiquitin-proteasome pathway, which may improve treatment outcomes by inducing cancer cell death and enhancing the effectiveness of existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular targets and targeted therapies for malignant mesothelioma. Palumbo, C., Bei, R., Procopio, A., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

CD30 is a potential therapeutic target in malignant mesothelioma. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Mesothelin Immunotherapy for Cancer: Ready for Prime Time? [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Molecular targets and targeted therapies for malignant mesothelioma. [2021]