Pembrolizumab After Radiation Therapy in Treating Patients With Pleural Malignant Mesothelioma

NCT02959463 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 2015-0856NCI-2016-01923
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best way to give pembrolizumab after radiation therapy in treating patients with pleural malignant mesothelioma. Radiation therapy uses high energy radiation to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab after radiation therapy may kill more tumor cells.

Conditions

Pleural Malignant Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Safety/Toxicity

  To determine the safety and tolerability of pembrolizumab administered after radiation therapy in patients with MPM. The primary endpoint was "unaccepable" high grade adverse events (AEs) from baseline to 4-month after the start of radiation therapy.

  Baseline to 4-months after the start of radiation therapy

Secondary Outcomes (2)

• Overall Survival (OS)

  Every 6 weeks (42 +/- 7 days) until to 48 weeks, then every 12 weeks (+/- 7 days) to 5 years

• Progression-Free Survival (PFS)

  Every 6 weeks (42 +/- 7 days) until to 48 weeks, then every 12 weeks (+/- 7 days) to 5 years

Study Arms (2)

Cohort 1 (hemithoracic radiation therapy, pembrolizumab)

EXPERIMENTAL

Patients undergo hemithoracic radiation therapy. After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy

Cohort 2 (palliative radiation therapy, pembrolizumab)

EXPERIMENTAL

Patients undergo palliative radiation therapy over 1-3 weeks to only the region of palliation (a region that does not include the entire side of the chest or thorax). After radiation therapy, patients receive pembrolizumab IV over about 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Radiation: Palliative Radiation Therapy; Biological: Pembrolizumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort 1 (hemithoracic radiation therapy, pembrolizumab); Cohort 2 (palliative radiation therapy, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Cohort 1 (hemithoracic radiation therapy, pembrolizumab); Cohort 2 (palliative radiation therapy, pembrolizumab)

Palliative Radiation Therapy RADIATION

Undergo palliative radiation therapy

Cohort 2 (palliative radiation therapy, pembrolizumab)

Radiation Therapy RADIATION

Undergo hemithoracic radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Cohort 1 (hemithoracic radiation therapy, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Be willing and able to provide written informed consent/assent for the trial
• 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
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>=1,500 /mcL (within 10-15 days of treatment initiation)
• Platelets \>= 100,000 /mcL (within 10-15 days of treatment initiation)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (within 10-15 days of treatment initiation)
• 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 (within 10-15 days of treatment initiation)
• Serum total bilirubin =\< 1.5 X ULN or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (within 10-15 days of treatment initiation)
• 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 (within 10-15 days of treatment initiation)
• Albumin \>= 2.5 mg/dL (within 10-15 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10-15 days of treatment initiation)
• 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 (within 10-15 days of treatment initiation)
• 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
• 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

You may not qualify if:

• 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
• Has a diagnosis of immunodeficiency; note that patients should not receive steroids during pembrolizumab administration
• Has a known history of active tuberculosis (TB) (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• 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
• 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)
• 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
• 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
• 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 (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• 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
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

pembrolizumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Matthew Stephen Ning, MD, MPH
• Organization: The University of Texas MD Anderson Cancer Center

msning@mdanderson.org

(832) 710-8779

Study Officials

• Matthew Ning, MD, MPH

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2016
• First Posted: November 9, 2016
• Study Start: May 1, 2017
• Primary Completion: November 15, 2024
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 6, 2026
• Results First Posted: November 13, 2025

Record last verified: 2026-02

Locations

US (1)