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

Conditions:Lung Cancer, Lung Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:December 20, 2017
End Date:December 2020
Contact:Andreas Rimner, MD

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An Efficacy and Safety Study of Avelumab Plus SBRT in Malignant Mesothelioma (MPM)

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.

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

- No plans for surgical resection.

- At least one prior line of systemic therapy. Note: Patients on prior immunotherapy are

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

- 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)

- 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 (i.e., ≥ Grade 1 at baseline) from adverse events due to agents

2. Prior chemotherapy, targeted small molecule therapy, within 4 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) within 4 weeks prior to study Day 1 or has
not recovered (i.e., >/= Grade 1 at baseline) 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

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. 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
We found this trial at
Middletown, New Jersey 07748
Phone: 212-639-6025
Middletown, NJ
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Basking Ridge, New Jersey 07920
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Basking Ridge, NJ
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Commack, New York 11725
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Commack, NY
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500 Westchester Avenue
Harrison, New York 10604
Phone: 212-639-6025
Harrison, NY
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1275 York Ave
New York, New York 10021
(212) 639-2000
Principal Investigator: Andreas Rimner, MD
Phone: 212-639-6025
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
New York, NY
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Rockville Centre, New York 11570
Phone: 212-639-6025
Rockville Centre, NY
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Uniondale, New York 11553
Phone: 212-639-6025
Uniondale, NY
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