Prospective Observation of Failure Patterns in NSCLC Treated With ICIs

July 29, 2020 updated by: Zhengfei Zhu, Fudan University

Prospective Observational Study of Failure Patterns in Non-small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors

By prospectively observing the time to the best therapeutic effect of non-small cell lung cancer after ICI treatment, the characteristics of lesion distribution when the best therapeutic effect is reached, and the phenotype of disease progression after ICI treatment response, the investigators intended to explore the failure pattern of NSCLC after the once effective ICI treatment. The investigators also aim to evaluate the feasibility and clinical value of radiotherapy for the treatment of oligo-progressive lesions after ICI.

Study Overview

Status

Not yet recruiting

Study Type

Observational

Enrollment (Anticipated)

320

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

    • Shanghai
      • Shanghai, Shanghai, China, 200031
        • Fudan University Shanghai Cancer Center
        • 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 to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

stage IV NSCLC developing acquired resistance under ICI treatment.

Description

Inclusion Criteria (Part I):

  • Age between 18 and 75 years.
  • ECOG PS 0-1.
  • Pathologically confirmed stage IV NSCLC.
  • Negative for driver genes including EGFR, ALK, and ROS-1.
  • Patients achieved PR or CR after ICI treatment, as defined by RECIST 1.1.
  • Patients with complete radiological information of baseline lesions.
  • Life expectancy of more than 3 months.
  • Ability to understand and willingness to provide the informed consent.

Exclusion Criteria (Part I):

  • Severe autoimmune disease or other contradictions to ICI treatment.
  • Mixed small cell with non-small cell lung cancer histology.
  • Driver gene positive, including EGFR, ALK, and ROS-1.
  • Pregnant or lactating women.
  • History of any other malignancy.
  • Active infection, congestive heart failure, myocardial infarction within the 6 months prior to enrollment, unstable angina pectoris or cardiac arrhythmia.
  • Patients receiving immunosuppressive agents,or other investigational treatment. Long-term corticosteroid users are also excluded.
  • Mental disorders, drug abuse, and social condition that may negatively impact compliance in the opinion of the investigator.

Inclusion Criteria (Part II, patients with OPD):

  • Patients with oligo-progression disease (1-3 progression lesions in 1-2 organs) when developing acquired resistance to ICI.
  • Radiotherapy to at least one of the OPD lesions is indicated in the opinion of the investigator. At least one of the irradiated lesion(s) should be evaluable according to RECIST 1.1.
  • ECOG PS 0-2.
  • Life expectancy of more than 3 months.
  • Complete radiological information of all lesions during the follow-up.
  • Patients with a prior history of surgery are eligible if they have recovered adequately from the toxicity and/or complications of surgery.
  • Adequate bone marrow function within 1 week prior to the enrollment: hemoglobin ≥80g/L, white blood cell (WBC) count ≥ 4.0 * 10 ^ 9/L or neutrophil count ≥ 1.5 * 10 ^ 9/L, and platelet count ≥ 100 * 10 ^ 9/L;
  • Ability to understand and willingness to provide the informed consent.

Exclusion Criteria (Part II):

  • Secondary malignancy.
  • Histology transformation to non-NSCLC.
  • Ineligible for radiotherapy in the opinion of the investigator. Or none of the OPD are evaluable by RECIST 1.1.
  • ECOG PS 3 or worse.
  • Short life expectancy (less than 3 months).
  • Unable to provide complete radiological information of lesions.
  • Inadequate bone marrow function.
  • Cannot understand or unwilling to provide the informed consent.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oligo-progression disease rate in NSCLC patients developing acquired resistance to ICI treatment.
Time Frame: at least 2 months after ICI treatment.

Acquired resistance (AR) was defined as disease progression after partial or complete response (PR or CR) to ICI treatment. (by RECIST standard v1.1)

When observing disease progression in ICI treatment, the number and distribution of progression lesions were recorded.

Oligo-progression disease (OPD) was defined as 1-3 progression lesions in 1-2 organs. The OPD rate in all AR cases will be calculated.

at least 2 months after ICI treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Adverse Events
Time Frame: Two years
Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.
Two years
Overall objective response rate to radiotherapy.
Time Frame: at least 4 weeks after radiotherapy.
When radiotherapy to at least one of the OPD lesions is indicated in the opinion of the investigator. Overall objective response rate (ORR) to radiotherapy will be recorded. ORR was defined as the proportion of participants with partial response (PR) or complete response (CR) to treatment as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
at least 4 weeks after radiotherapy.
Objective response rate in non-irradiated lesion
Time Frame: at least 4 weeks after radiotherapy.
Objective response rate (ORR) in Non-irradiated Lesion was defined as the proportion of patients with at least 30% reduction from baseline in the longest diameter of any of non-irradiated target lesions defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time-point from the date of treatment initiation to the date of last follow-up.
at least 4 weeks after radiotherapy.
Overall Survival since AR development.
Time Frame: Two years
OS was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.
Two years

Collaborators and Investigators

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

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 (Anticipated)

September 1, 2020

Primary Completion (Anticipated)

August 31, 2023

Study Completion (Anticipated)

August 31, 2025

Study Registration Dates

First Submitted

July 27, 2020

First Submitted That Met QC Criteria

July 27, 2020

First Posted (Actual)

July 30, 2020

Study Record Updates

Last Update Posted (Actual)

July 31, 2020

Last Update Submitted That Met QC Criteria

July 29, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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