Photodynamic Therapy to Amplify the Response to Immunotherapy in Patients With Non-small Cell Lung Cancer With Pleural Disease

June 1, 2023 updated by: Roswell Park Cancer Institute

Utilizing Photodynamic Therapy to Amplify the Response to Immunotherapy in Patients With Non-Small Cell Lung Cancer (NSCLC) With Pleural Disease or Malignant Pleural Mesothelioma (MPM) - Phase I Study

This phase I trial evaluates the side effects of intraoperative photodynamic therapy with porfimer sodium in enhancing the response to immunotherapy with an immune checkpoint inhibitor drug in patients with non-small cell lung cancer with pleural disease. Photodynamic therapy is a technique that that works by combining a photosensitizing agent (porfimer sodium in this trial) and an intense light source to kill tumor cells. Photodynamic therapy may decrease the patients' symptoms and improve their quality of life.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Principal Investigator:
          • Saikrishna S. Yendamuri
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed non-small cell lung cancer (NSCLC) with pleural disease and PDL1 expression < 50% or histologically confirmed diagnosis of malignant pleural mesothelioma not candidates for macroscopic complete resection
  • Adequate blood tests 14 days prior to intraoperative PDT and with values within the ranges specified below.

    • Hemoglobin ≥ 9.0 g/L
    • Absolute neutrophil count ≥ 1.5 x 10^9/L
    • Platelets ≥ 100 x 10^9/L
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except participants with Gilbert's Syndrome, who are eligible with bilirubin ≤ 2.5 ULN)
    • Alanine transaminase ≤ 2.5 xupper limit of normal (ULN), unless liver metastases or invasion are present, in which case it must be ≤ 5 x ULN
    • Aspartate aminotransferase ≤ 2.5 x ULN, unless liver metastases or invasion are present, in which case it must be ≤ 5 x ULN
  • The patient is on standard of care immunotherapy or combination of chemotherapy and immunotherapy with no evidence of progression or a candidate for chemoimmunotherapy as determined by the treating medical oncologist. Eligible patients that are currently on standard of care treatment will have the systemic therapy paused for 4-6 weeks prior to the surgery and intraoperative PDT and will resumed within 4-12 weeks after surgery following standard of care timeframe utilized for restarting systemic therapy after major surgical procedures to ensure adequate post-op recovery and tissue healing.
  • Age >= 18 years old
  • Life expectancy of at least 12 weeks.
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) score of 0 - 1
  • Subjects of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for 6 months after surgery. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • The subject must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent prior to receiving any study related procedure
  • Platelet count < 100,000

Exclusion Criteria:

  • Patients who received chemotherapy, chemoimmunotherapy or radiotherapy within <4 weeks (6 weeks for nitrosoureas or mitomycin C) or those who have not recovered from reversible adverse events prior to the scheduled surgery and intraoperative PDT.
  • Patients with untreated or symptomatically unstable treated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treated and stable brain metastases (at least 28 days from last radiotherapy treatment) are eligible as long as steroids are not required for symptom management
  • Patients with porphyria, or with known hypersensitivity to porphyrins or porphyrin-like compounds

    • Absolute neutrophil count < 1500
    • Left ventricular ejection fraction (LVEF) < lower level of normal (LLN)
    • Total bilirubin > 2 mg/dL
    • Creatinine clearance < 60 mL/min (Cockcroft Gault equation)
    • Alkaline phosphatase (hepatic) > 3 times the upper normal limit (SGPT) > 3 times the upper normal limit
    • NOTE: Roswell Park clinical lab blood chemistry is performed on plasma unless otherwise indicated
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or nursing female subjects
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the Investigator's opinion deems the subject an unsuitable candidate to receive porfimer sodium such as active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:

    • Patients with vitiligo or alopecia
    • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
    • Any chronic skin condition that does not require systemic therapy
    • Patients without active disease in the last 5 years may be included
    • Patients with celiac disease controlled by diet alone
  • Patients with Hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Exceptions include past or resolved Hepatitis B (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) and patients positive for hepatitis C (HCV) antibody if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in absence of clinical suspicion of HIV
  • Received an investigational agent within 30 days prior to enrollment
  • History of, or active autoimmune disorder, requiring systemic steroids or immunosuppressive agents. Exceptions allowed: patients with autoimmune dermatologic conditions not requiring systemic steroids or immunosuppressive agents (e.g. vitiligo, eczema, etc.), endocrine-related autoimmune conditions receiving appropriate hormonal supplementation. Use of immunosuppressant drugs such as steroids, azathioprine, tacrolimus, cyclosporine, etc. is not permitted within 4 weeks before recruitment (exception allowed is use of steroids as hormone replacement therapy or as supportive medication e.g. anti-emesis, contrast allergy, pre-medication, etc. or other short-course therapy less than 2 weeks continuously within 4 weeks of study treatment)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (porfimer sodium, photodynamic therapy)
Patients receive porfimer sodium IV over 3-5 minutes 24-48 hours prior to standard of care VATS, followed by photodynamic therapy
Given IV
Other Names:
  • CL-184116
  • Dihematoporphyrin Ester
  • Photofrin II
  • 87806-31-3
Undergo VATS
Other Names:
  • VATS
Undergo photodynamic therapy
Other Names:
  • PDT
Subjects will receive one course of light therapy at the time of surgery
Other Names:
  • intra-operative photo dynamic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of serious adverse events (SAE)
Time Frame: 28 days post study-related immunotherapy
Will be determined by recording the occurrence of SAE during the first 28 days post study-related immunotherapy. The SAE will be evaluated using the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
28 days post study-related immunotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: assessed up to 2 years
Will utilize Kaplan-Meier curves to descriptively examine dose level differences and generate summary statistics.
assessed up to 2 years
Overall survival (OS)
Time Frame: assessed up to 2 years
Will utilize Kaplan-Meier curves to descriptively examine dose level differences and generate summary statistics.
assessed up to 2 years
Changes in the immune phenotype of peripheral blood CD8+ T cells
Time Frame: Baseline up to 2 years
Will be analyzed using a repeated measures analysis-of-variance (ANOVA) model with a factor for dose level time and a dose level by time interaction.
Baseline up to 2 years
Changes in platelet-to-lymphocyte ratio
Time Frame: Baseline up to 2 years
Will be analyzed using a repeated measures ANOVA model with a factor for dose level, time and a dose level by time interaction.
Baseline up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: • Saikrishna Yendamuri, MD, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2022

Primary Completion (Estimated)

March 15, 2025

Study Completion (Estimated)

March 15, 2025

Study Registration Dates

First Submitted

April 5, 2021

First Submitted That Met QC Criteria

April 5, 2021

First Posted (Actual)

April 8, 2021

Study Record Updates

Last Update Posted (Actual)

June 2, 2023

Last Update Submitted That Met QC Criteria

June 1, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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