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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug brentuximab vedotin can treat mesothelioma when surgery isn't an option. Brentuximab vedotin is a monoclonal antibody designed to stop cancer cells from growing and spreading. The trial targets people with mesothelioma who have a specific protein marker on their cancer cells, known as CD30+. It may suit those diagnosed with mesothelioma that can't be surgically removed and who have had little or no success with previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that brentuximab vedotin is likely to be safe for humans?

Research has shown that brentuximab vedotin is generally well-tolerated by patients. Studies on individuals with CD30 positive malignant mesothelioma, a type of cancer that cannot be surgically removed, have assessed its safety. Patients receive close monitoring for any side effects.

Brentuximab vedotin is a monoclonal antibody, designed to target specific cells, such as cancer cells. While all treatments can have side effects, research indicates that brentuximab vedotin's side effects are manageable for many patients. These studies help ensure that any serious issues are quickly identified and addressed.

Since this treatment has reached phase 2 trials, initial safety checks have been completed. Phase 2 trials focus more on the treatment's effectiveness, but they still closely monitor safety. If serious side effects were common, the treatment likely would not have reached this stage. Always consult a healthcare provider to understand what joining a trial might mean. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Brentuximab vedotin is unique because it targets cancer cells differently than standard mesothelioma treatments. While most treatments like chemotherapy affect both healthy and cancerous cells, brentuximab vedotin uses an antibody-drug conjugate approach. This means it specifically targets a protein called CD30 on cancer cells, delivering a powerful drug directly to them and sparing more healthy cells. Researchers are excited about this targeted approach as it could lead to fewer side effects and more effective treatment outcomes for patients with inoperable mesothelioma.

What evidence suggests that brentuximab vedotin might be an effective treatment for inoperable mesothelioma?

Research shows that brentuximab vedotin, the treatment under study in this trial, may help treat a type of mesothelioma that surgery cannot remove. This treatment uses monoclonal antibodies to stop cancer cells from growing and spreading. Previous studies found that patients using this drug controlled the disease for about four months, indicating it can slow cancer progression. Brentuximab vedotin targets a specific protein, CD30, on cancer cells, making it a precise treatment. While more research is needed, these early results suggest it could be a helpful option for those with inoperable mesothelioma. ^{1 2 3 4 6}

Who Is on the Research Team?

Anne S. Tsao

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03007030

Brentuximab Vedotin in Treating Patients With CD30+ ... This phase II trial studies how well brentuximab vedotin works in treating patients with CD30 positive (+) malignant mesothelioma that cannot be removed by ...

2. withpower.com withpower.com/trial/phase-3-mesothelioma-malignant-3-2017-8c526

Brentuximab Vedotin for Inoperable Mesothelioma This phase II trial studies how well brentuximab vedotin works in treating patients with CD30 positive (+) malignant mesothelioma that cannot be removed by ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8505556/

Biological basis for novel mesothelioma therapies - PMC In a large phase III trial (Mesothelioma Avastin Cisplatin Pemetrexed Study, MAPS) of 448 patients, median OS was increased from 16.1 to 18.8 months [90], which ...

4. lanierlawfirm.com lanierlawfirm.com/mesothelioma/cancer/treatment/clinical-trials/

Mesothelioma Clinical Trials The 4-month disease control rate in patients with malignant pleural mesothelioma who are treated with brentuximab vedotin. The response rate, progression-free ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/disease/mesothelioma/treatment?pn=1

Treatment Clinical Trials for Mesothelioma - NCI Brentuximab Vedotin in Treating Patients with CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery. Status: Active. Location: M D Anderson Cancer ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/search?q=malignant%20mesothelioma

malignant mesothelioma Clinical Research Trials To evaluate the response rate, progression-free and overall survival, and safety/toxicity of brentuximab vedotin in CD30+ malignant mesothelioma. II. To ...