Clinical Trial: A Randomized Two Arm Phase II Trial of Pembrolizumab Alone or Sequentially Following Single Fraction Non-ablative Radiation to One of the Target Lesions, in Previously Treated Patients With Stage IV NSCLC

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Trial of Pembrolizumab Sequentially Following Single Fraction Non-ablative Radiation to One of the Target Lesions, in Previously Treated Patients With Stage IV

Brief Summary: This study looks at patients with advanced lung cancer. Participants in this study will be randomized into two groups. The first group will have radiation plus a drug (pembrolizumab). The second group will have only the drug (pembrolizumab). Tumors of participants will be measured to see if the addition of radiation changes the growth of the tumor compared to the drug alone.

Detailed Summary:

This is a Phase 2 randomized two arm phase II trial of pembrolizumab alone or sequentially following focal radiation to one of the target lesions, in previously treated patients with stage IV Non-Small Cell Lung Cancer (NSCLC). The primary goal of this trial is to compare the efficacy of focal radiation (RT) to an index lesion as a way of enhancing the anti-tumor immune response to pembrolizumab to that of pembrolizumab alone. The primary efficacy endpoint is overall RECIST-defined response outside the radiation field. To accomplish this goal 66 patients will be randomized 2:1 (stratified by histology (squamous versus non-squamous) and refractory versus non-refractory disease) to radiation plus pembrolizumab or pembrolizumab only, respectively.

Primary Objective: To determine the tumor responses outside the radiation field (abscopal effect) after radiation followed by pembrolizumab in metastatic NSCLC.

Secondary Objectives:

  1. To determine the progression-free and overall survival in patients with NSCLC receiving pembrolizumab, who receive Single Fraction Radiation Therapy (SFRT)
  2. To determine the safety and toxicity of the combination of SFRT and pembrolizumab
  3. To examine potential predictive biomarkers in tumor samples and peripheral blood in patients treated with pembrolizumab and SFRT
  4. To determine the local control of SFRT in the radiated lesion, when SFRT is given with pembrolizumab
  5. To evaluate the induction of a T-cell response in patients with metastatic NSCLC treated with radiation and the effect of radiation

Sponsor: Case Comprehensive Cancer Center

Current Primary Outcome: Number of patients with each response as measured by RECIST 1.1 [ Time Frame: From first visit to disease progression, up to 24 months after beginning treatment ]

The Best Overall Response is the best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The anti-tumor activity will be evaluated as an efficacy endpoints based on radiographic (CT or PET/CT). RECIST 1.1 will be applied for evaluation of tumor response.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Median time of progression free survival [ Time Frame: From first visit to disease progression, up to 24 months after beginning treatment ]
    Progression free survival, PFS is defined as the time from initiation of study drug post-SFRT, until the first documented, confirmed progression of disease. PFS will also be measured and report from the initiation of study drug, pre-SFRT.
  • Median time of overall survival [ Time Frame: From first visit to disease progression, up to 24 months after beginning treatment ]
    Overall Survival, OS will be measure from the initiation of study therapy
  • Number of patients with local control of disease with SFRT [ Time Frame: From first visit to disease progression, up to 24 months after beginning treatment ]
    Local Control with SFRT: The target lesion selected for SFRT will be followed for local control. For the purpose of the study, local control will be defined as a complete response, partial response, or stable disease within the planning target volume.
  • Duration of local control of disease with SFRT [ Time Frame: From first visit to disease progression, up to 24 months after beginning treatment ]
    Local Control with SFRT: The target lesion selected for SFRT will be followed for local control. For the purpose of the study, local control will be defined as a complete response, partial response, or stable disease within the planning target volume. The duration of local control will be measured from the time of SBRT treatment fraction.


Original Secondary Outcome: Same as current

Information By: Case Comprehensive Cancer Center

Dates:
Date Received: January 14, 2016
Date Started: May 11, 2017
Date Completion: December 2018
Last Updated: May 15, 2017
Last Verified: May 2017