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Stereotactic Body Radiation Therapy and Avelumab Immunotherapy for Treatment of Malignant Mesothelioma

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ClinicalTrials.gov Identifier: NCT03399552
Recruitment Status : Recruiting
First Posted : January 16, 2018
Last Update Posted : January 29, 2018
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to find out whether the combination of avelumab and 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.

Condition or disease Intervention/treatment Phase
Malignant Mesothelioma (MPM) Drug: Avelumab Radiation: Stereotactic Body Radiation Therapy Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single-arm, two-stage study that will be conducted at Memorial Sloan Kettering Cancer Center Main Campus and regional sites.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Efficacy and Safety Study of Avelumab Plus SBRT in Malignant Mesothelioma (MPM)
Actual Study Start Date : December 20, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma
Drug Information available for: Avelumab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Avelumab
The treatment will consist of one dose of avelumab every other week as well as a short course of SBRT after the first two doses of avelumab.
Drug: Avelumab
10mg/kg delivered by IV infusion
Radiation: Stereotactic Body Radiation Therapy
short course of SBRT after the first two doses of avelumab

Primary Outcome Measures :
  1. Overall response rate [ Time Frame: 3 years ]
    defined by modified RECIST 1.1 for mesothelioma

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient willing and able to provide written informed consent for the trial.
  • Patient age ≥ 18 at time of consent.
  • Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma (MPM).
  • No plans for surgical resection.
  • At least one prior line of systemic therapy including platinum and pemetrexed.
  • At least one targetable lesion appropriate for palliative SBRT and one non-target lesion
  • Karnofsky Performance Score (KPS) ≥ 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, defined as:

    • Absolute Neutrophil Count ≥ 1.5K/mcL.
    • Platelet count ≥ 100K/mcL.
    • Adequate renal function as defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤ 1.5 x ULN
    • Hemoglobin > 9g/dL (prior transfusion permitted)
    • Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
    • AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
  • 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 Criteria:

  • 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 medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
  • Prior Therapies:

    1. Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to agents administered > 4 weeks earlier.
    2. Prior chemotherapy, targeted small molecule therapy, within 3 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to a previously administered agent (excluding Grade 2 neuropathy).
    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 ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • 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 (Tuberculosis).
    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. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
    9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  • Pregnant women or women who are breastfeeding or of childbearing potential and not using a highly effective method of birth control for at least one month prior to enrollment. If the risk of contraception exists, male and female subjects must use highly effective contraception throughout the study and for at least 60 days after last avelumab treatment.

    a. Highly effective contraception includes either 2 barrier methods (diaphragm, condom by the partner, copper intrauterine device, sponge, or spermicide), or 1 barrier method and 1 hormonal method (any oral, subcutaneous, intrauterine, or intramuscular registered and marketed contraceptive agent that contains an estrogen and/or a progesterone agent).

  • Vaccination 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 (>10 mg/day prednisone or equivalent), methotrexate, azathioprine, and tumor necrosis factor alpha (TNF-α) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03399552

Contact: Andreas Rimner, MD 212-639-6025 rimnera@mskcc.org
Contact: Marjorie Zauderer, MD 646-888-4656

United States, New Jersey
Memorial Sloan Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Andreas Rimner, MD    212-639-6025      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Andreas Rimner, MD    212-639-6025      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Andreas Rimner, MD    212-639-6025      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Andreas Rimner, MD    212-639-6025      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Andreas Rimner, MD    212-639-6025      
Contact: Majorie Zauderer, MD    646-888-4656      
Principal Investigator: Andreas Rimner, MD         
Memorial Sloan Kettering Rockville Centre Recruiting
Rockville Centre, New York, United States, 11570
Contact: Andreas Rimner, MD    212-639-6025      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Principal Investigator: Andreas Rimner, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03399552     History of Changes
Other Study ID Numbers: 17-358
First Posted: January 16, 2018    Key Record Dates
Last Update Posted: January 29, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Stereotactic Body Radiation Therapy
Avelumab Immunotherapy

Additional relevant MeSH terms:
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs