We encourage participation in clinical trials for research leading to a cure for mesothelioma. It is known that nationally the statistics for participation in adult cancer trials is between 3-5% of adults who have a cancer diagnosis.

For mesothelioma patients and families that are interested in clinical trials, researching clinical trials and eligibility can be a time-consuming barrier to participation. The information about clinical trials is available on www.clinicaltrials.gov

Our goal is to feature one mesothelioma clinical trial monthly and break it down to understandable terms, to decipher the eligibility requirements, and to possibly encourage participation in these trials.

The official title to the Clinical Trial; Stereotactic Body Radiation Therapy and Avelumab Immunotherapy for Treatment of Malignant Mesothelioma.

Purpose: The purpose of this study is to find out whether the combination of avelumab and Stereotactic Body Radiation Therapy- SBRT is safe and what effect avelumab has on mesothelioma when given in combination with SBRT. In addition, a goal of this protocol is to study the effect of radiation therapy on the immune system.  It is thought that radiation treatment may create a form of “vaccine” against cancer inside the body and immunotherapy may improve this effect. The combination of radiation treatment and immunotherapy may be more effective against cancer than either radiation or immunotherapy alone.

Sponsor: Memorial Sloan Kettering Cancer Center in collaboration with Pfizer.

Start Date: December 20, 2017

Completion Date: December 2020

Estimated Enrollment: 27 participants

How it Works: Treatment consists of one dose of avelumab every other week as well as a short course of SBRT after the first two doses of avelumab. The drug, avelumab is delivered by IV infusion. The SBRT is given after the first two doses of avelumab.

Criteria:

Inclusion:  Over age 18

      Be willing and able to provide written informed consent

Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma.

No plans for surgical resection

At least one prior line of systemic therapy. Patients on prior immunotherapy are eligible.

At least one targetable lesion appropriate for palliative SBRT and one non-target lesion.

Karnofsky Performance Score > 70%

If of childbearing potential, must be willing to use highly effective mode of contraception

For at least one month prior, during, and for 2 months after the end of active therapy

Adequate organ function demonstrated by lab tests- see www.clinicaltrials.gov  for parameters

If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.   

Exclusion:

Currently participating and receiving another study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

Prior radiation therapy precluding SBRT

Continuous oxygen use

Current use of immunosuppressive medications- for exceptions see www.clinicaltrials.gov

Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.

Known prior severe hypersensitivity to investigational product or Ny component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies.

Patient who rapidly progressed on prior immunotherapy, as determined by the treating physician, are not eligible.

Prior Therapies:

1. Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has not recovered from adverse events due to agents administered.
2. Prior chemotherapy, targeted small molecule therapy, within 4 weeks prior to study Day 1 or has not recovered from adverse events due to previously administered agent.
3. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte- associated antigen-4 (CTLA-4) antibody (including ipiliumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) within 4 weeks prior to study Day 1or has not recovered from adverse events.

Comorbidities or Prior Conditions

1. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
2. Prior organ transplantation including allogenic stem-cell transplantation.
3. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
4. Known history of active TB
5. Known history of HIV or known acquired immunodeficiency syndrome.
6. Active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening or positive serologies indicating prior infection.
7. Active infection requiring systemic therapy.
8. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
9. Clinically significant cardiovascular disease, cerebro vascular accidents/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrythmia requiring medication.

Pregnant women or women who are breastfeeding or of childbearing potential and not using a highly effective means of birth control.

Vaccinations within 4 weeks prior to the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines.

Concomitant use of the following medications

1. Any investigational anticancer therapy
2. Any concurrent chemotherapy, immunotherapy, or biologic therapy.  Concurrent use of hormones for non-cancer related conditions (e.g. Insulin for diabetes and hormone replacement therapy) is acceptable.
3. Immunosuppressive medications including, but not limited to systemic corticosteroids, methotrexate, azathioprine, and tumor necrosis factor alpha blockers. Use of immunosuppressive medications for the management of investigational product-related AEs, in subjects with contrast allergies is acceptable. In addition, use of inhaled and intranasal corticosteroids is permitted.

Known contraindications to radiotherapy.

Definitions from www.cancer.gov

With any clinical trial, all participation is voluntary.  Before enrollment a detailed consent form will be reviewed with the participant and signed.  The participant can withdraw from a clinical trial at any point in time. Think about participating if able, the only way to progress to a cure for mesothelioma is through clinical trials.

Immunotherapy

A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies.

Stereotactic Body Radiation Therapy

A type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue.

Avelumab

A drug used with axitinib to treat advanced renal cell carcinoma (a type of kidney cancer) that has not already been treated. It is also used to treat urothelial carcinoma (a type of bladder cancer) that is locally advanced or has spread to other parts of the body. It is used in patients whose disease got worse during or after treatment with anticancer drugs that included platinum. Avelumab is also used to treat Merkel cell carcinoma (a rare type of skin cancer) that has spread to other parts of the body. It is also being studied in the treatment of other types of cancer. Avelumab binds to a protein called PD-L1, which is found on some cancer cells. Avelumab may block PD-L1 and help the immune system kill cancer cells. It is a type of monoclonal antibody and a type of immune checkpoint inhibitor. Also called Bavencio.

Immune system

A complex network of cells, tissues, organs, and the substances they make that helps the body fight infections and other diseases. The immune system includes white blood cells and organs and tissues of the lymph system, such as the thymus, spleen, tonsils, lymph nodes, lymph vessels, and bone marrow.