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

NCT02658097 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE1516
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stage IV Non-Small Cell Lung Cancer

Keywords

Lung Cancer; pembrolizumab; focal radiation; RT

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Each Response as Measured by RECIST 1.1

  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.

  From first visit to disease progression, up to 24 months after beginning treatment

Secondary Outcomes (4)

• Median Time of Progression Free Survival

  From first visit to disease progression, up to 24 months after beginning treatment

• Median Time of Overall Survival

  From first visit to disease progression, up to 24 months after beginning treatment

• Number of Patients With Local Control of Disease With SFRT

  From first visit to disease progression, up to 24 months after beginning treatment

• Duration of Local Control of Disease With SFRT

  From first visit to disease progression, up to 24 months after beginning treatment

Other Outcomes (2)

• Number of Patients With Pneumonitis

  From first visit to 30 days after disease progression, up to 25 months after beginning treatment

• Changes in PD-L1

  From first visit to 30 days post treatment, up to 25 months

Study Arms (1)

Single Fraction Radiation Therapy (SFRT) + pembrolizumab

EXPERIMENTAL

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

Drug: Pembrolizumab; Radiation: Single Fraction Radiation Therapy

Interventions

Pembrolizumab DRUG

200mg Pembrolizumab by IV infusion

Single Fraction Radiation Therapy (SFRT) + pembrolizumab

Single Fraction Radiation Therapy RADIATION

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

Also known as: SFRT, RT

Single Fraction Radiation Therapy (SFRT) + pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor and primary investigator.
• Have a performance status of ≤1 ECOG Performance Scale.
• Demonstrate adequate organ function
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9g/dL
• Serum creatinine or measured ≤1.5 times the upper limit of normal (ULN) or measured or calculated creatinine clearance ≥ 60 mL/min for subjects with creatinine levels \>1.5 times the institutional ULN
• Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 times ULN or ≤ 5 times ULN for subjects with liver metastases
• Albumin ≥ 2.5 mg/dL
• Have one measurable lesion of at least 1 cm outside the planned radiation field (defined as not receiving direct beam from any of the treatment portals).
• 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 must be willing to use an adequate method of contraception - Contraception, for the course of the study through 120 days after the last dose of study medication.

You may not qualify if:

• 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 or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active 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 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.
• Patient who have previously received radiation overlapping with the current planned radiation treatment fields are ineligible. Overlap is defined as any tissue falling within the direct path of both prior and current planned radiation fields.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Patients with active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of pembrolizumab.
• Has had prior chemotherapy, within 2 weeks prior to study treatment. Patients on targeted therapy (tyrosine kinase inhibitor) may go on the study after 5 days off therapy.
• Patients who have not recovered (i.e., ≤ Grade 2 or at baseline) from adverse events due to a previously administered agent.
• 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 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44118, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Nathan Pennell
• Organization: Cleveland Clinic, Case Comprehensive Cancer Center

TaussigResearch@ccf.org

1-866-223 8100

Study Officials

• Nathan Pennell, MD, PhD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 18, 2016
• Study Start: June 7, 2017
• Primary Completion: February 26, 2022
• Study Completion: March 10, 2023
• Last Updated: May 3, 2024
• Results First Posted: May 3, 2024

Record last verified: 2024-05

Locations

US (1)