Clinical trial NCT04492969: Prospective Observation of Failure Patterns in NSCLC Treated With ICIs
Official title: Prospective Observational Study of Failure Patterns in Non-small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: NSCLC Stage IV
NSCLC, Recurrent
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-07-30
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: stage IV NSCLC developing acquired resistance under ICI treatment.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Oligo-progression disease rate in NSCLC patients developing acquired resistance to ICI treatment.
timeFrame: at least 2 months after ICI treatment.
Secondary outcomes:
measure: Overall objective response rate to radiotherapy.
timeFrame: at least 4 weeks after radiotherapy.
measure: Objective response rate in non-irradiated lesion
timeFrame: at least 4 weeks after radiotherapy.
measure: Percentage of Participants With Adverse Events
timeFrame: Two years
measure: Overall Survival since AR development.
timeFrame: Two years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhengfei Zhu, MD
role: PRINCIPAL_INVESTIGATOR
References: