Trial of Consolidation Pembrolizumab After Concurrent Chemotherapy and Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer

Phase II Trial of Consolidation Pembrolizumab After Concurrent Chemotherapy and Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer

The main purpose of this study is to assess the safety, tolerability and anti-tumor activity of the experimental study drug pembrolizumab (also known as Keytruda or MK-3475) in people with non-small cell lung cancer (NSCLC) that has come back after radiation therapy.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic or cytologic diagnosis of NSCLC who have received previous intrathoracic radiation therapy with definitive intent and have a tumor recurrence in or near the prior irradiation fields. Re-biopsy of the recurrence is not required and is left to the discretion of the treating physician, although every effort should be made to confirm recurrence pathologically.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Age 18 or greater
• Patients with prior invasive malignancies are allowed, provided they have been treated with definitive intent and have no evidence of active disease requiring treatment in the past 2 years.
• Patients must be capable of giving informed consent and be willing and able to comply with schedule.
• Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN.
• Platelets >100,000 cells/mm3 and ANC > 1,250 cells/mm3
• Creatinine ≤ 1.5 X ULN OR measured or calculated creatinine clearance ≥50 mL/min for subject with creatinine levels > 1.5 X institutional ULN. (GFR can also be used in place of creatinine or CrCl).
• Clinical target volume (CTV) size must be <250 cc, no more than 74 Gy of prior radiation in 2 Gy fractions previously administered.

Exclusion Criteria:

• Allergy to Pembrolizumab or related compounds
• History of symptomatic CTCAEv4 grade ≥3 pneumonitis following the initial course of definitive radiation therapy
• History of symptomatic idiopathic pulmonary fibrosis or interstitial lung disease
• Use of continuous oxygen
• Diagnosis of immunodeficiency or exposure to systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. (Nasal or oral inhalers are permissible).
• 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 are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome are not excluded from the study.
• History of allogenic tissue or solid organ transplant
• Progression while on prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Patients with known extrathoracic metastases, including brain metastases, or known malignant pleural or pericardial effusion
• Prior radiation treatment less than 6 months from the planned start of reirradiation of any part of the intended treatment volume
• Pregnant or breast-feeding patients. Men and women of reproductive potential may not participate in this study unless they have agreed to use an effective contraceptive method while in this study.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Known active Hepatitis B (e.g., HBsAg positive or HBV DNA detectable) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Single Arm, Open Label	Drug: Pembrolizumab; Concurrent Pembrolizumab after proton reirradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Progression Free Survival	Progression Free Survival is defined as the time from initiation of definitive therapy to the first documented disease progression per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 based on radiologists' review or death due to any cause, whichever occurs first, or last patient follow-up that documented lack of disease progression. Patients who have not had disease progression or who have died, will be censored on the most recent clinical evaluation date that documented that they were progression-free.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced a Grade 3+ Adverse Event	Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. Adverse events were reviewed by the treating physicians and principal investigator to assess potential attribution to reirradiation/chemotherapy or pembrolizumab.	2 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Steven Feigenberg, MD, Abramson Cancer Center at Penn Medicine

Publications and helpful links

General Publications

• Yegya-Raman N, Berman AT, Ciunci CA, Friedes C, Berlin E, Iocolano M, Wang X, Lai C, Levin WP, Cengel KA, O'Reilly SE, Cohen RB, Aggarwal C, Marmarelis ME, Singh AP, Sun L, Bradley JD, Plastaras JP, Simone CB 2nd, Langer CJ, Feigenberg SJ. Phase 2 Trial of Consolidation Pembrolizumab After Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2023 Aug 29:S0360-3016(23)07846-X. doi: 10.1016/j.ijrobp.2023.08.047. Online ahead of print.

Helpful Links

• Phase II trial of consolidation pembrolizumab after proton reirradiation for thoracic recurrences of non-small cell lung cancer: Pembro after PBT ReRT for NSCLC

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2017
• Primary Completion (Actual): September 12, 2023
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease Attributes; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: UPCC 16516

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No