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Pleural Malignant MesotheliomaPhase 1NCT02959463

Pembrolizumab After Radiation Therapy in Treating Patients With Pleural Malignant Mesothelioma

A Phase 1 study testing Laboratory Biomarker Analysis, Palliative Radiation Therapy and Pembrolizumab in people with Pleural Malignant Mesothelioma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pleural Malignant Mesothelioma
What is being tested?
Laboratory Biomarker Analysis, Palliative Radiation Therapy and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
1 May 2017to 27 Apr 2026
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • 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
  • COHORT 1 (PATIENTS RECEIVING HEMITHORACIC RADIATION THERAPY)
  • Patients must not have evidence of metastatic disease per positron emission tomography (PET)/ computed tomography (CT) scan; mediastinal lymph node involvement is acceptable
  • Patients will have received at least 2 cycles of induction chemotherapy with pemetrexed/cisplatin or pemetrexed/carboplatin
  • Forced expiratory volume in 1 second (FEV1) >= 30% of predicted postoperative (ppoFEV1, as if patient underwent a pneumonectomy)
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) > 35% predicted
  • 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
  • COHORT 2 INCLUSION CRITERIA
  • 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
  • Any prior number of prior therapies, including prior immunotherapy, is allowed
  • Patient must have prior treatment with a platinum plus pemetrexed regimen

Who cannot join

  • 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)
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  • 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)
  • 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
  • Evidence of interstitial lung disease
  • COHORT 1 EXCLUSION CRITERIA
  • Patients undergoing an extrapleural pneumonectomy (EPP); lung sparing surgeries, such as pleurectomy/decortication, are acceptable
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • COHORT 2 EXCLUSION CRITERIA
  • Patients in which hemithoracic radiation therapy is planned
  • Patients who have received EPP for mesothelioma
  • COHORTS 1 AND 2 EXCLUSION CRITERIA
  • Patients with inherited syndromes associated with hypersensitivity to ionizing radiation, specifically patients with known history of ataxia-telengiectasia, Nijmegen breakage syndrome

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I Trial of Adjuvant Pembrolizumab After Radiation Therapy for Lung-Intact Malignant Pleural Mesothelioma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and tolerability of pembrolizumab administered after radiation therapy in patients with malignant pleural mesothelioma (MPM) who have not undergone extrapleural pneumonectomy.

SECONDARY OBJECTIVES:

  1. To assess progression-free and overall survival (progression free survival [PFS] and overall survival [OS], respectively) in patients receiving pembrolizumab after radiation therapy for malignant pleural mesothelioma (MPM).

EXPLORATORY OBJECTIVES:

  1. To evaluate biomarkers of interest, including cytokines, measurements of T-cell activation, and serum exosome micro ribonucleic acid (RNA)s with the delivery of pembrolizumab after radiation therapy for MPM.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients undergo hemithoracic radiation therapy.

COHORT 2: 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, both cohorts receive pembrolizumab intravenously (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.

After completion of study treatment, patients are followed up at 30 days, every 6 weeks for 48 weeks, then every 12 weeks for up to 5 years.

Being tested
Laboratory Biomarker Analysis, Palliative Radiation Therapy, Pembrolizumab, Radiation Therapy
Medical subject headings
Mesothelioma, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Palliative Radiation TherapyRadiation

    Undergo palliative radiation therapy

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation

    Undergo hemithoracic radiation therapy

Study groups in NCT02959463
Study groupRoleWhat they receive
Cohort 1 (hemithoracic radiation therapy, pembrolizumab)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy
Cohort 2 (palliative radiation therapy, pembrolizumab)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Radiation: Palliative Radiation Therapy; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to 4-months after the start of radiation therapy

Secondary outcomes (2)

  1. Overall Survival (OS)

    To assess overall survival (OS) in patients receiving Pembrolizumab after radiation therapy for MPM.

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

  2. Progression-Free Survival (PFS)

    To assess progression-free survial (PFS) in patients receiving Pembrolizumab after radiation therapy for MPM.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2016 (estimated)
  2. Study start1 May 2017
  3. Primary completion15 Nov 2024
  4. Study completion27 Apr 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02959463
Sponsor's protocol ID
2015-0856
Other IDs
NCI-2016-01923, 2015-0856
Status last verified
May 2026
First submitted
7 Nov 2016
Last updated
27 May 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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