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

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.

Tracking Information
First Received DateNovember 7, 2016
Last Changed DateJune 14, 2017
Start DateMay 1, 2017
Anticipated Primary Completion DateMay 2020
Primary Outcome Measures

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]

Treatment-Related Toxicity of Adding Pembrolizumab with Radiation Therapy in Participants who Have Possibly Received Prior Chemotherapy and No Surgery [Time Frame: 4 months]

Secondary Outcome Measures

Tumor Response [Time Frame: 12 weeks last dose of Pembrolizumab]

Descriptive Information
PhasePhase 1
Study TypeInterventional
Condition
  • Malignant Pleural Mesothelioma
Intervention
  • Radiation: Hemithoracic Radiation Therapy
  • Radiation: Palliative Radiation Therapy
  • Drug: Pembrolizumab
Study Arms / Comparison Groups2 / 0
Detailed Description

Study Groups:

If participant is found to be eligible to take part in this study, participant will be assigned to 1 of 2 groups. Participant's doctor will decide which group participant is in. Up to 12 participants will be enrolled in each group.

If participant is enrolled in Group A, participant will have already received at least 2 cycles of chemotherapy and possibly lung-sparing surgery. Participant will then receive radiation therapy to one side of participant's chest, or thorax, a technique called "hemithoracic radiation." Participant will then receive pembrolizumab.

If participant is enrolled in Group B, participant may or may not have had chemotherapy or immunotherapy. Participant will not have received surgery. Participant will receive radiation therapy over a course of 1-3 weeks to a region that does not include the entire side of participant's chest, or thorax. Participant will then receive pembrolizumab.

Study Drug Administration:

In both groups, participant will receive pembrolizumab by vein over about 30 minutes on Day 1 of each 3-week cycle after radiation therapy, for up to 2 years.

Study Visits:

When participant is not receiving radiation, participant will have these visits about every 3 weeks while participant receives immunotherapy:

- Participant will have a physical exam.

- Blood (about 1-2 tablespoons) will be drawn to check participant's immune system, for side effects, and to check the status of the disease.

Participant will have a CT and/or PET scan to check the status of the disease before radiation therapy, at Cycle 4, and then every 3 cycles thereafter. If the doctor thinks it is needed, participant may have extra imaging.

Participant will have a PFT to check participant's lung function at Cycle 7 and then every 6 cycles.

End-of-Study Visit:

When participant stops receiving the study drug:

- Participant will have a physical exam.

- Blood (about 1-2 tablespoons) will be drawn to check participant's immune system, for side effects, and to check the status of the disease.

- Participant will have a PFT to check participant's lung function.

Length of Study:

Participant may continue taking the study drug for up to 2 years. Participant will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if participant is unable to follow study directions.

If the disease appears to be getting worse or the tumors appear to be getting larger, participant may still be able to receive the study drug if participant and participant's doctor decide it is in participant's best interest. Sometimes the disease appears to get worse but the study drug is actually working.

However, there are risks of continuing to receive the study drug because the disease may actually be getting worse. Participant is still at risk for side effects due to the study drug. This could also delay starting other treatments. The disease may get worse to the point that participant is no longer able to receive other treatments.

If participant chooses to receive the study drug after the disease gets worse, participant will continue to have study visits as described above. The study doctor will discuss this option with participant.

Participation on the study will be over after the follow-up visits.

Follow Up:

About 30 days after participant's last dose of study drug, participant will have a physical exam.

About every 12 weeks after participant's last dose of pembrolizumab:

- Participant will have a physical exam.

- Participant may have CT or PET scans to check the status of the disease.

- If participant's doctor thinks it is needed, blood (about 1 tablespoon) may be drawn for routine tests.

- At Weeks 12 and 24, participant will have PFTs performed.

If participant is unable to make these visits, participant will be contacted by phone to check participant's health.

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.

Recruitment Information
Recruitment StatusRecruiting
Anticipated Enrollment24
GenderAll
Ages18 Years - N/A
Accepts Healthy VolunteersNo
Contact Daniel Gomez, MD
Email: CR_Study_Registration@mdanderson.org
Phone: 713-563-2300
Eligibility Criteria

Inclusion Criteria:

1. Patients must have a histologic diagnosis of malignant pleural mesothelioma

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 disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

5. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from Merck.

6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

7. Demonstrate adequate organ function as described, all screening labs should be performed within 10 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 /=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN;

8. Inclusion #6 continued--HEPATIC: Serum total bilirubin 1.5 ULN; aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) /= 2.5 mg/dL; COAGULATION: International Normalized Ratio (INR) or Prothrombin Time (PT)

9. 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.

10. 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.

11. 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.

12. *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.

13. 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.

14. *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 must have prior treatment with a platinum plus 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.,

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 (

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 P/D or 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.

Administrative Information
NCTIDNCT02959463
Responsible Party,
SponsorM.D. Anderson Cancer Center
Verification DateJune 2017
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