Trials / Active Not Recruiting

Active Not RecruitingNCT02444741

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

Status: Active Not Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 126 (actual)

Sponsor: M.D. Anderson Cancer Center · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and toxicity profile of intravenous MK-3475 (pembrolizumab) administered in combination with stereotactic body radiation therapy (SBRT) targeting 1-4 liver or thoracic lesion(s) in patients with metastatic non-small cell lung cancer (NSCLC). (Phase I) II. To evaluate the safety and toxicity profile of intravenous MK-3475 administered in combination with non-stereotactic wide-field radiation therapy (WFRT) targeting 1-4 liver or thoracic lesion(s) in patients with metastatic NSCLC. (Phase I) III. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of MK-3475 and SBRT combination therapy. (Phase I) IV. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of MK-3475 and WFRT combination therapy. (Phase I) V. To determine the rate of out-of-field objective responses (either complete response \[CR\] or partial response \[PR\]) of the non-irradiated disease sites. (Phase II) SECONDARY OBJECTIVE: I. To determine whether the addition of radiation therapy (XRT) to MK-3475 can improve the progression free survival (PFS) rate compared to MK-3475 alone. (Phase II) OUTLINE: This is a phase I, dose-escalation study of pembrolizumab followed by a phase II study. PHASE I: Patients are assigned to 1 of 2 treatment groups. GROUP I: Patients who exhibit a lung lesion of size and location amenable to SBRT receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also receive SBRT in 4 fractions daily on days 2-5 or either intensity modulated radiation therapy (IMRT), proton beam radiation therapy (PBRT), or 3 dimensional conformation radiation therapy (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 II: Patients 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 concurrent with pembrolizumab administration. PHASE II: Patients for whom SBRT is recommended are randomized to Group 1 or 2, patients for whom conventional radiation therapy is recommended are randomized to Group 3 or 4, and patients with lesions amenable to SBRT or WFRT are assigned to Group 5. GROUP I: Patients 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: Patients 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 progressive disease (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: Patients 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: Patients 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 immune response related criteria (irRC) then XRT will be delivered after the third dose of pembrolizumab, while patients with stable disease (SD) or PR will not start XRT and will continue to be followed. These patients will then have follow up computed tomography (CT) scans 5 weeks after course 3 three 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: Patients 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. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Conditions

Interventions

Type	Name	Description
RADIATION	3-Dimensional Conformal Radiation Therapy	Undergo 3D-CRT
RADIATION	Intensity-Modulated Radiation Therapy	Undergo IMRT
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Pembrolizumab	Given IV
RADIATION	Proton Beam Radiation Therapy	Undergo PBRT
RADIATION	Radiation Therapy	Undergo low dose radiation therapy
RADIATION	Stereotactic Body Radiation Therapy	Undergo SBRT

Timeline

Start date: 2015-09-17
Primary completion: 2026-09-30
Completion: 2026-09-30
First posted: 2015-05-14
Last updated: 2025-10-09

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02444741. Inclusion in this directory is not an endorsement.