Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Erythema Multiforme

Erythema

Skin Diseases

Skin Diseases, Vesiculobullous

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

200mg Pembrolizumab by IV infusion on day 1 of each 3 week cycle. 8Gy will be given in a single fraction on the first day of treatment

8Gy radiation therapy will be given in a single fraction on the first day of treatment

Single Fraction Radiation Therapy

Nathan Pennell, MD, PhD

The goal of this clinical trial is to determine if low single palliative dose radiation to the lung cancer will improve your immune response against the tumor and if sequential treatment with pembrolizumab (the study drug) would offer superior results compared to pembrolizumab alone in participants with non-small cell lung cancer.

The purpose of this research is also to study whether there are any changes present in the DNA, RNA, and proteins of a participant's tumor or the blood cells that may contribute to a response to the study treatment or progression of cancer. This research may help researchers in the future to learn more about the causes, risks, treatments, or prevention of cancers or other health problems.

Participants will consent to a screening period, a core or treatment phase, and a post-study observation phase. During the screening phase, participants will undergo a series of tests to determine if they are eligible for the study. The core study period, or treatment period, will start with a single dose of radiation and then continue for the first eight treatments of pembrolizumab, approximately 24-28 weeks. Participants will have a new biopsy taken after two treatments of the study drug. Following the 24-28 week treatment cycle, if the cancer is responding to treatment, the participant's physician will continue to treat with pembrolizumab as a standard treatment. Following treatment, the post-study observation phase will monitor participant response to drugs and outcomes.

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.

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

Pembrolizumab Alone or Sequentially Following Single Fraction Non-ablative Radiation to One of the Target Lesions, in Previously Treated Patients With Stage IV NSCLC

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 NSCLC

For patients receiving SFRT to lung lesions, the development of grade 3 or greater pneumonitis that is probably or definitely attributable to either SFRT or pembrolizumab within the follow-up period will be monitored

From first visit to disease progression, up to 25 months after beginning treatment. Median (95% CI) overall survival by PD-L1 status in months.

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. RECIST 1.1 criteria are as follows: Complete Response (CR) is defined as the disappearance of all lesions and pathologic lymph nodes; Partial Response (PR) is ≥ 30% decrease in sum of diameters with no new lesions, no progression of non-target lesions; Stable disease(SD) is defined as no PR - no progressive disease; and Progressive Disease (PD) is defined as ≥ 20% increase compared to smallest sum of diameters in study or progression of non-target lesions or new lesions.

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.

Overall Survival, OS will be measure from the initiation of study therapy

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.

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.

Case Comprehensive Cancer Center

200mg Pembrolizumab by IV infusion on day 1 of each 3 week cycle. 8Gy will be given in a single fraction on the first day of treatment

Pembrolizumab: 200mg Pembrolizumab by IV infusion

Single Fraction Radiation Therapy: 8Gy radiation therapy will be given in a single fraction on the first day of treatment

Single Fraction Radiation Therapy (SFRT) + Pembrolizumab

40-49 years of age

50-59 years of age

60-69 years of age

70-79 years of age

80-89 years of age

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Former Smoker

The number of prior treatments each participant were underwent before enrolling in this clinical trial.

Prior Treatment

Carboplatin/Abraxane

Carboplatin/Pemetrexed

Cisplatin/Alimta

ETOPOSIDE / CARBOPLATIN 21 DAY

Maintenance Pemetrexed

Pemetrexed + Bevacizumab

Rucaparib

SBRT

The types of prior treatments that participants received prior to enrolling in this clinical trial.

Spots Global Cancer Trial Database for single fraction radiation therapy