Observational Retro-prospective Study on PD1/PDL1 Inhibitors Treatment Duration in Patients With NSCLC (I-STOP)

September 15, 2023 updated by: University of Milano Bicocca

Observational Retro-prospective Study on Programmed Cell Death 1/ Programmed Cell Death Ligand1 (PD1/PDL1) Inhibitors Treatment Duration in Patients With Non Small Cell Lung Carcinoma

Retrospective/ prospective, multicentre, international observational study on long-responders with non-small cell lung carcinoma patients treated with anti Programmed cell Death 1/ Programmed cell Death Ligand 1 (anti-PD1/PD-L1) in any line of treatment for at least 24 months with response partial/complete response or disease stability. Patients will be divided into two cohorts based on whether they stopped treatment at 24 months (not for toxicity) or continued by clinical choice and stratified according to treatment line and baseline PD-L1 expression.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Programmed cell Death protein / Ligand 1 (PD-1 / PD-L1) inhibitors Atezolizumab, Nivolumab and Pembrolizumab have demonstrated a great efficacy and a good safety profile in patients with Non-Small Cell Lung Cancer (NSCLC), both in first-line (PD-L1 expression > 50%) and in subsequent lines regardless of PD-L1 status. Recently, the combination of Pembrolizumab with platinum salts and pemetrexed has become the gold standard for the first-line treatment in patients with PD-L1 expression <50%. Data on the optimal duration of immunotherapy are scarce, especially considering that the onset of immune-related adverse events (irAE) has also been reported after several months of treatment and the long-term effects of the persistent immune system stimulation are unknown. Furthermore, predictive factors are not available to identify those patients who will respond to treatment and could benefit from a shorter duration of therapy -this information is pivotal to minimize the risk of side effects and improve the quality of life. Basal characteristics, such as PD-L1 expression, percentage of Cluster of Differentiation 8 (CD-8) + T-lymphocyte in tumor-infiltrating lymphocytes (TILs), mutational status, neutrophil to lymphocyte ratio (NLR), and platelets to lymphocytes ratio (PLR) have been reported as possible biomarkers, but further data are needed to confirm their predictive value. The purpose of the study is to identify the differences in terms of effectiveness and safety of immunotherapy in long-responder patients in the two cohorts. Secondary objectives are to evaluate the outcome after anti-PD1/PD-L1 rechallenge or other treatment for patients who progress after immunotherapy discontinuation and to identify baseline characteristics that may be predictive of response (molecular characteristics, biohumoral parameters, body mass index).

Study Type

Observational

Enrollment (Estimated)

300

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 Contact Backup

Study Locations

  • Italy
      • Ancona, Italy
        • Recruiting
        • AOU Ospedali Riuniti
        • Contact:
          • Rossana Berardi
      • Firenze, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Careggi
        • Contact:
          • Francesca Mazzone
      • Genova, Italy
        • Recruiting
        • Ospedale Policlinico San Martino
        • Contact:
          • Carlo Genova
      • Modena, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria
        • Contact:
          • Federica Bertolini
      • Monza, Italy, 20900
      • Napoli, Italy
        • Recruiting
        • Istituto Nazionale dei Tumori
        • Contact:
          • Alessandro Morabito
      • Orbassano, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria San Luigi
        • Contact:
          • Simona Carnio
      • Parma, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria
        • Contact:
          • Alessandro Leonetti
      • Pesaro, Italy
        • Recruiting
        • Azienda Ospedaliera Marche Nord
        • Contact:
          • Rita Chiari
      • Udine, Italy
        • Recruiting
        • Azienda Sanitaria Universitaria Friuli Centrale
        • Contact:
          • Marianna Macerelli

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

Sampling Method

Probability Sample

Study Population

The study population consists of NSCLC patients treated for at least 24 months with Pembrolizumab, Nivolumab or Atezolizumab in any treatment line. The patients should obtain and maintain a partial (RP) or complete response (RC) or stable disease (SD) at the end of the 24-month therapy.

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Histologically / cytologically confirmed diagnosis of NSCLC, with or without brain metastases
  3. Illness measurable according to Response Evaluation Criteria in Solid Tumours (iRECIST) criteria
  4. At least 24 months of treatment with Pembrolizumab, Nivolumab or Atezolizumab
  5. Complete response (CR)/ partial response (RP)/ stable disease at the end of 24-month treatment. The maintenance of the response may also have been obtained after loco-regional treatment, e.g. surgery or radiotherapy, in the case of oligoprogression for a maximum of 3 locoregional treatments (e.g. radiotherapy, surgery) throughout the period of treatment and suspension. Even progression at the brain level, treated with radiation therapy or surgery, can be considered, provided that it is followed by a disease control for at least 3 months.
  6. At least 3 months of follow-up or death within three months after stopping the 24-month treatment.
  7. Informed consent freely granted and acquired before the start of the study, for alive and contactable patients.

Exclusion Criteria:

  1. Initial chemo-immunotherapy treatment or association with other immunotherapy or other drugs in the context of clinical trials.
  2. Permanent discontinuation of treatment with anti PD-1 / PD-L1 for adverse events.
  3. More than 3 loco-regional treatments for maintaining the radiological response
  4. Suspension of immunotherapy for a period longer than 40 days during the 24-month 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

  • Observational Models: Cohort
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cohort 1
The cohort includes patients who discontinue the treatment at 24 months and continue the follow-up at least for 3 months
Drug: Immunotherapy
At least 24 months with Pembrolizumab, Nivolumab or Atezolizumab in any treatment line
Other Names:
  • Pembrolizumab
  • Atezolizumab
  • Nivolumab
Cohort 2
The cohort includes patients who continue the treatment beyond 24 months until unacceptable toxicity or progression.
Drug: Immunotherapy
At least 24 months with Pembrolizumab, Nivolumab or Atezolizumab in any treatment line
Other Names:
  • Pembrolizumab
  • Atezolizumab
  • Nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free survival
Time Frame: Through study completion, an average of 18 months
Progression free survival (PFS) in the two cohorts; at least 24 months with Pembrolizumab, Nivolumab or Atezolizumab in any treatment line
Through study completion, an average of 18 months
Overall survival
Time Frame: Through study completion, an average of 18 months
Overall survival (OS) in the two cohorts; OS will be calculated from the first day of treatment until the date of death from any cause.
Through study completion, an average of 18 months
Percentage of patients with disease progression after 24 months of treatment
Time Frame: Through study completion, an average of 18 months
Proportion of patients who show disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria
Through study completion, an average of 18 months

Collaborators and Investigators

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

Sponsor

University of Milano Bicocca

Collaborators

Azienda Ospedaliera San Gerardo di Monza

Investigators

  • Principal Investigator: Diego Cortinovis, MD, Fondazione IRCCS San Gerardo dei Tintori, Monza

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)

May 19, 2022

Primary Completion (Estimated)

November 30, 2024

Study Completion (Estimated)

November 30, 2024

Study Registration Dates

First Submitted

May 27, 2022

First Submitted That Met QC Criteria

June 9, 2022

First Posted (Actual)

June 14, 2022

Study Record Updates

Last Update Posted (Actual)

September 18, 2023

Last Update Submitted That Met QC Criteria

September 15, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I-STOP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data will be available upon request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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