Pembrolizumab and Stereotactic Body Radiation Therapy or Non-Stereotactic Wide-Field Radiation Therapy in Treating Patients With Non-small Cell Lung Cancer
Phase I/II Trial of MK-3475 and Hypofractionated Stereotactic Radiation Therapy in Patients With NSCLC
2 other identifiers
interventional
126
1 country
1
Brief Summary
This randomized phase I/II trial studies the side effects and best dose of pembrolizumab when given together with stereotactic body radiation therapy or non-stereotactic wide-field radiation therapy (conventional radiation therapy) and to see how well they work in treating patients with non-small cell lung cancer. 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pembrolizumab together with radiation therapy may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2015
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 12, 2015
CompletedFirst Posted
Study publicly available on registry
May 14, 2015
CompletedStudy Start
First participant enrolled
September 17, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2026
October 9, 2025
October 1, 2025
11 years
May 12, 2015
October 7, 2025
Conditions
Outcome Measures
Primary Outcomes (5)
Disease response, according to immune related response criteria (Phase I/II)
Treatment success will be defined as radiographic complete response or partial response measured using Pearson chi-squared or Fisher exact tests.
Beginning 3 months after initiation of treatment
Incidence of toxicity (Phase I/II)
Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Up to 90 days after completion of treatment
Maximum tolerated dose of pembrolizumab and stereotactic body radiation therapy (Phase I)
Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
22 days
Maximum tolerated dose of pembrolizumab and non-stereotactic wide-field radiation therapy (Phase I)
Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
22 days
Objective response (complete response + partial response) of the non-irradiated disease sites, according to Out-Field immune related response criteria (Phase II)
Assesed according to Out-Field immune related response criteria. Treatment success will be defined as radiographic complete response or partial response measured using Pearson chi-squared or Fisher exact tests.
Up to 5 years
Secondary Outcomes (2)
Progression-free survival (Phase II)
From the time of enrollment to first evidence of progressive disease, assessed at 3 months after treatment initiation
Overall survival
Receipt of the first pembrolizumab dose to death, assessed up to 5 years
Study Arms (7)
Group I, Phase I (pembrolizumab + SBRT)
EXPERIMENTALPatients who exhibit a lung lesion of size and location amenable to SBRT receive pembrolizumab IV over 30 minutes on day 1. Patients also receive SBRT in 4 fractions daily on days 2-5 or either IMRT, PBRT, or 3D-CRT in 15 fractions total concurrent with pembrolizumab administration on days 1-19. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Group I, Phase II (pembrolizumab + SBRT)
EXPERIMENTALPatients who exhibit a lung lesion with size and location amenable to SBRT receive pembrolizumab IV on day 1 and SBRT on days 44-47 or IMRT, PBT, or 3D-CRT on days 43-61. Treatment with pembrolizumab repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Group II, Phase I (pembrolizumab + IMRT, PBRT or 3D-CRT)
EXPERIMENTALPatients who exhibit a lung lesion of size or location not amenable to SBRT, but amenable to WFRT receive pembrolizumab as in Group I and either IMRT, PBRT, or 3D-CRT in 15 fractions total on days 1-19 concurrent with pembrolizumab administration.
Group II, Phase II (pembrolizumab + XRT upon PD)
EXPERIMENTALPatients who exhibit a lung lesion with size and location amenable to SBRT receive pembrolizumab IV as in Group I without XRT. At the first planned efficacy evaluation (5 weeks), patients exhibiting PD are treated with SBRT concurrent with the remaining cycles of pembrolizumab. In the event that lesion size has progressed to the point where the attending physician no longer considers SBRT safe, then the patient will be salvaged with IMRT, PBRT, or 3D-CRT and analyzed as part of the fourth treatment group.
Group III, Phase II (pembrolizumab + IMRT, PBRT, or 3D-CRT)
EXPERIMENTALPatients who exhibit a lung lesion with size and location not amenable to SBRT, but amenable to WFRT receive pembrolizumab IV as in Group I and IMRT, PBRT, or 3D-CRT on days 43-61.
Group IV, Phase II (pembrolizumab + XRT upon PD)
EXPERIMENTALPatients who exhibit a lung lesion with size and location not amenable to SBRT, but amenable to WFRT receive pembrolizumab IV as in Group I without XRT. The decision on when to start XRT will be assessed first at week 5 (after the second dose of pembrolizumab). If a patient has PD based on irRC then XRT will be delivered after the third dose of pembrolizumab, while patients with SD or PR will not start XRT and will continue to be followed. These patients will then have follow up CT scans 5 weeks after course 3 and then approximately every 3 months for the remainder of the trial; any patient at this point with PD will then have XRT delivered with the sixth dose of pembrolizumab.
Group V, Phase II (low dose radiation therapy)
EXPERIMENTALPatients with lesions amenable to SBRT or WFRT receive pembrolizumab IV as in Group I. Patients also receive either IMRT, PBRT, or 3D-CRT in 15 fractions to the primary lesions and low dose radiation therapy to other lesions on days 43-61 or SBRT in 4 fractions to primary lesions and low dose radiation therapy to other lesions on days 44-47.
Interventions
Undergo 3D-CRT
Undergo IMRT
Correlative studies
Given IV
Undergo PBRT
Undergo low dose radiation therapy
Undergo SBRT
Eligibility Criteria
You may qualify if:
- Pathologically confirmed non-small lung cancer; for patients in group 5, any solid tumor histology to be included
- Stage IV metastatic disease (only during the phase II)
- At least one thoracic or liver lesion amenable to radiation, for group 5 we need one area that can safely receive SBRT or WFRT, not restricted to lung or liver sites
- At least one additional non-contiguous lesion to the irradiated lesion amenable to radiographic evaluation
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable disease based on immune related response criteria (irRC) criteria
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) \>= 1,500 /mcL (performed within 28 days prior to study registration up to the first dose of study drug)
- Platelets \>= 100,000 /mcL (performed within 28 days prior to study registration up to the first dose of study drug)
- Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (performed within 28 days prior to study registration up to the first dose of study drug)
- 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 calculated creatinine clearance \[CrCl\]) or \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (creatinine clearance should be calculated per institutional standard) (performed within 28 days prior to study registration up to the first dose of study drug)
- Serum total bilirubin =\< 1.5 X ULN or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (performed within 28 days prior to study registration up to the first dose of study drug)
- 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 (performed within 28 days prior to study registration up to the first dose of study drug)
- International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days prior to study registration up to the first dose of study drug)
- 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 (performed within 28 days prior to study registration up to the first dose of study drug)
- +5 more criteria
You may not qualify if:
- Is currently participating in or has participated in a study of an investigational agent (except glutamine) or using an investigational device within 4 weeks of the first dose of treatment or 5 half lives, whichever is shorter
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; unless the steroid therapy is for physiological replacement
- Has a diagnosis of active scleroderma, lupus, or other autoimmune disease which by the opinion of the treating radiation oncologist precludes safe radiation therapy
- Has had prior radiation therapy to all available thoracic and liver lesions such that additional radiation therapy is unsafe by the opinion of the treating radiation oncologist
- Has had a prior monoclonal antibody within 4 weeks or 5 half-lives, which ever is shorter, 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 or targeted small molecule therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
- Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has a 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
- 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
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy or hospital admission
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (4)
Butner JD, Martin GV, Wang Z, Corradetti B, Ferrari M, Esnaola N, Chung C, Hong DS, Welsh JW, Hasegawa N, Mittendorf EA, Curley SA, Chen SH, Pan PY, Libutti SK, Ganesan S, Sidman RL, Pasqualini R, Arap W, Koay EJ, Cristini V. Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling. Elife. 2021 Nov 9;10:e70130. doi: 10.7554/eLife.70130.
PMID: 34749885DERIVEDTheelen WSME, Chen D, Verma V, Hobbs BP, Peulen HMU, Aerts JGJV, Bahce I, Niemeijer ALN, Chang JY, de Groot PM, Nguyen QN, Comeaux NI, Simon GR, Skoulidis F, Lin SH, He K, Patel R, Heymach J, Baas P, Welsh JW. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2021 May;9(5):467-475. doi: 10.1016/S2213-2600(20)30391-X. Epub 2020 Oct 20.
PMID: 33096027DERIVEDWelsh J, Menon H, Chen D, Verma V, Tang C, Altan M, Hess K, de Groot P, Nguyen QN, Varghese R, Comeaux NI, Simon G, Skoulidis F, Chang JY, Papdimitrakopoulou V, Lin SH, Heymach JV. Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial. J Immunother Cancer. 2020 Oct;8(2):e001001. doi: 10.1136/jitc-2020-001001.
PMID: 33051340DERIVEDChen D, Menon H, Verma V, Guo C, Ramapriyan R, Barsoumian H, Younes A, Hu Y, Wasley M, Cortez MA, Welsh J. Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials. J Immunother Cancer. 2020 Jan;8(1):e000492. doi: 10.1136/jitc-2019-000492.
PMID: 31996395DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
James Welsh
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 12, 2015
First Posted
May 14, 2015
Study Start
September 17, 2015
Primary Completion (Estimated)
September 30, 2026
Study Completion (Estimated)
September 30, 2026
Last Updated
October 9, 2025
Record last verified: 2025-10