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

NCT03399552

Last updated date
Study Location
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Malignant Mesothelioma (MPM)
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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. Note: Patients on prior immunotherapy are eligible.

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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
administered


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
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. 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

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Malignant Mesothelioma (MPM)Stereotactic Body Radiation Therapy and Avelumab Immunotherapy for Treatment of Malignant Mesothelioma
NCT03399552
  1. Uniondale, New York
  2. Basking Ridge, New Jersey
  3. Middletown, New Jersey
  4. Commack, New York
  5. Harrison, New York
  6. New York, New York
  7. Rockville Centre, New York
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Stereotactic Body Radiation Therapy and Avelumab Immunotherapy for Treatment of Malignant Mesothelioma
Official Title  ICMJE An Efficacy and Safety Study of Avelumab Plus SBRT in Malignant Mesothelioma (MPM)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE Malignant Mesothelioma (MPM)
Intervention  ICMJE
  • Drug: Avelumab
    10mg/kg delivered by IV infusion
  • Radiation: Stereotactic Body Radiation Therapy
    short course of SBRT after the first two doses of avelumab
Study Arms  ICMJE 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.
Interventions:
  • Drug: Avelumab
  • Radiation: Stereotactic Body Radiation Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 10, 2020)
15
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2018)
36
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Note: Patients on prior immunotherapy are eligible.
  • 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)
  • 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 administered
    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 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. 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-?) 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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03399552
Other Study ID Numbers  ICMJE 17-358
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Andreas Rimner, MDMemorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP