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Adjuvant Pembrolizumab After Radiation Therapy for Lung-Intact Malignant Pleural Mesothelioma

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ClinicalTrials.gov Identifier: NCT02959463
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to assess the safety of pembrolizumab (also called MK-3475) after radiation therapy (with or without surgery and/or chemotherapy) in patients with MPM.

This is an investigational study. Radiation therapy is delivered using FDA-approved and commercially available methods for local control of metastatic and primary tumors. Pembrolizumab is FDA approved and commercially available for the treatment of unresectable or metastatic melanoma, and for lung cancer. Its use in this study is investigational.

Up to 24 participants will take part in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Pleural Mesothelioma Radiation: Hemithoracic Radiation Therapy Radiation: Palliative Radiation Therapy Drug: Pembrolizumab Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Adjuvant Pembrolizumab After Radiation Therapy for Lung-Intact Malignant Pleural Mesothelioma
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: Prior Chemotherapy + Possible Lung-Sparing Surgery

Participants have already received at least 2 cycles of chemotherapy and possibly lung-sparing surgery.

Participants receive hemithoracic radiation therapy with intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) to a total dose of 45 Gy in 25 fractions to the entire hemithorax.

Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of each 3-week cycle after radiation therapy, for up to 2 years.

Radiation: Hemithoracic Radiation Therapy
Participants receive hemithoracic radiation therapy with intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) to a total dose of 45 Gy in 25 fractions to the entire hemithorax.
Other Names:
  • Radiation treatment
  • XRT
  • Intensity modulated radiation therapy
  • IMRT
  • Proton beam therapy
  • PBT

Drug: Pembrolizumab
200 mg by vein on Day 1 of each 3-week cycle after radiation therapy, for up to 2 years.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

Experimental: Possible Prior Chemo and No Surgery

Participants may or may not have had prior chemotherapy or immunotherapy. Participants have not received surgery.

Participants receive palliative radiation therapy over a course of 1-3 weeks to a region that does not include the entire side of the chest, or thorax.

Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of each 3-week cycle after radiation therapy, for up to 2 years.

Radiation: Palliative Radiation Therapy
Participants receive palliative radiation therapy over a course of 1-3 weeks to a region that does not include the entire side of the chest, or thorax. Participants receive either 3 Gy x 10 fractions = 30 Gy, or 4 Gy x 5 fractions = 20 Gy, or 5 Gy x 5 fractions = 25 Gy, or 45-52.5 Gy in 15 fractions. Participants treated using either IMRT or 3D conformal therapy.
Other Names:
  • XRT
  • Radiation treatment
  • Intensity modulated radiation therapy
  • IMRT
  • 3D conformal therapy

Drug: Pembrolizumab
200 mg by vein on Day 1 of each 3-week cycle after radiation therapy, for up to 2 years.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475




Primary Outcome Measures :
  1. Treatment-Related Toxicity of Adding Pembrolizumab with Radiation Therapy in Participants who Have Undergone at Least 2 Cycles of Chemotherapy and Possible Lung-Sparing Surgery [ Time Frame: 4 months ]
    If treatment-related toxicity rate is more than 30%, trial will stop.

  2. Treatment-Related Toxicity of Adding Pembrolizumab with Radiation Therapy in Participants who Have Possibly Received Prior Chemotherapy and No Surgery [ Time Frame: 4 months ]
    If treatment-related toxicity rate is more than 30%, trial will stop.


Secondary Outcome Measures :
  1. Tumor Response [ Time Frame: 12 weeks last dose of Pembrolizumab ]
    RECIST version 1.1 used for assessment of tumor response utilizing CT as preferred imaging technique in this study.



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Patients must have a histologic diagnosis of malignant pleural mesothelioma, with histologic diagnosis from the pleura or relevant lymph node stations, including mediastinal, hilar, or supraclavicular lymph nodes.
  2. Be willing and able to provide written informed consent/assent for the trial.
  3. Be >/= 18 years of age on day of signing informed consent.
  4. Have measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. However, note that patients in Cohort 1 that have undergone an R0 resection will be eligible for the trial.
  5. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  6. Demonstrate adequate organ function as described, all screening labs should be performed within 10-15 days of treatment initiation: HEMATOLOGICAL: Absolute neutrophil count (ANC) >/=1,500 /mcL; Platelets >/= 100,000 / mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment); RENAL: Serum creatinine </= 1.5 X upper limit of normal (ULN) or Measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)) >/=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN;
  7. Inclusion #6 continued--HEPATIC: Serum total bilirubin </= 1.5 X ULN or Direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN; aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) </= 2.5 X ULN or </= 5 X ULN for subjects with liver metastases; Albumin >/= 2.5 mg/dL; COAGULATION: International Normalized Ratio (INR) or Prothrombin Time (PT) </= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) </= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  9. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  10. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  11. *Additional Inclusion Criteria - COHORT 1 (Patients Receiving Hemithoracic Radiation Therapy): *1. Patients must not have evidence of metastatic disease per PET/CT scan. Mediastinal lymph node involvement is acceptable. *2. Patients will have received at least 2 cycles of induction chemotherapy with pemetrexed/cisplatin or pemetrexed/carboplatin. *3. The following pulmonary function tests are required: a. Forced expiratory volume in 1 second (FEV1)>/=30% of predicted postoperative (ppoFEV1, as if patient underwent a pneumonectomy) based on the following formula using a quantitative perfusion scan: Predicted post-resection FEV1=FEV1 x % perfusion to the uninvolved lung from the quantitative perfusion report. b. Diffusing capacity of the lungs for carbon monoxide (DLCO)>35% predicted.
  12. Continued Additional Inclusion Criteria - COHORT 1: Patients must be assessed to be a suitable candidate for hemithoracic radiation therapy per the treating radiation oncologist. If the patient undergoes pleurectomy/decortication, they must initiate hemithoracic radiation therapy within 4 months of the surgery date. Patients that do not meet the dose constraints outlined below will be removed from the study prior to radiation therapy.
  13. *Additional Inclusion Criteria - COHORT 2: *1. Patients must be assessed to be a suitable candidate for radiation therapy by the treating radiation oncologist. Patients that do not meet the dose constraints outlined below will be removed from the study prior to radiation therapy. *2. Any prior number of prior therapies, including prior immunotherapy, is allowed. *3. Patient has received prior treatment with a platinum-pemetrexed regimen.

Exclusion Criteria:

  1. Is currently participating and receiving 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.
  2. Has a diagnosis of immunodeficiency. Note that patients should not receive steroids during Pembrolizumab administration.
  3. Has a known history of active tuberculosis (TB) (Bacillus Tuberculosis)
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 and who have not recovered adequately from this treatment (</=Grade 2 toxicity at the time of enrollment).
  7. Has a known additional malignancy that is progressing or requires active treatment. Patients with a stage I-III cancer that has been cured over two years ago are not excluded in the study.
  8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  10. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  11. Has an active infection requiring systemic therapy.
  12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  15. Has known active Hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or Hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) [qualitative] is detected).
  16. Has received a live vaccine within 30 days of planned start of study therapy. *Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  17. Evidence of interstitial lung disease.
  18. *Additional Exclusion Criteria - COHORT 1: Patients undergoing an extrapleural pneumonectomy (EPP). Lung sparing surgeries, such as pleurectomy/decortication, are acceptable.
  19. Additional Exclusion Criteria - COHORT 1: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  20. Additional Exclusion Criteria - COHORT 2: *1. Patients in which hemithoracic radiation therapy is planned. *2. Patients who have received EPP for mesothelioma.
  21. Additional Exclusion Criteria - Cohorts 1 and 2: 1. Patients with inherited syndromes associated with hypersensitivity to ionizing radiation, specifically patients with known history of Ataxia-Telangiectasia, Nijmegen breakage syndrome.

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): NCT02959463


Contacts
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Contact: Daniel Gomez, MD 713-563-2300 dgomez@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       dgomez@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Daniel Gomez, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02959463     History of Changes
Other Study ID Numbers: 2015-0856
NCI-2016-01923 ( Registry Identifier: NCI CTRP )
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019

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

Keywords provided by M.D. Anderson Cancer Center:
Malignant pleural mesothelioma
MPM
Non-metastatic
Pembrolizumab
Keytruda
MK-3475
SCH-900475
Radiation therapy
Radiation treatment
XRT
Intensity modulated radiation therapy
IMRT
Proton beam therapy
PBT
3D conformal therapy

Additional relevant MeSH terms:
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Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents