This phase II trial finds out the effect of local consolidative therapy and durvalumab in treating patients with stage III non-small cell lung cancer that has 3 or fewer lesions of progression (oligoprogressive) and greater than 3 lesions of progression (polyprogressive) after chemoradiation and anti-PD-l1 therapy. Local consolidative therapy, such as surgery and/or radiation, after initial treatment may kill any remaining tumor cells. Immunotherapy with durvalumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving local consolidative therapy and durvalumab may help to control the disease.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
Stage III NSCLC (AJCC 7th and 8th edition) patients who received standard chemoradiation followed by durvalumab therapy with either progressive disease or persistent disease. Persistent disease defined as residual positron emission tomography (PET) avidity 6 months after completion of initial definitive therapy and confirmed with biopsy
For lung adenocarcinoma patients, patients must not harbor any EGFR sensitizing mutations, ALK fusion, ROS1 rearrangements, RET fusions, or MET exon 14 skipping mutations where there are standard of care therapy options available. For patients with histologies other than adenocarcinoma, EGFR and ALK status is not required. Adenocarcinoma patients may be consented prior to the EGFR, ALK, and ROS1 status being known, but EGFR, ALK, and ROS1 status must be determined prior to initiating therapy. EGFR, ALK, and ROS ALK status may be determined using either tumor- or plasma-based, Clinical Laboratory Improvement Act (CLIA)-certified assays. For patients with NSCLC, not otherwise specified (NOS), EGFR testing is not required, as the frequency of alterations is exceedingly rare in this histology
Cohort A: Oligoprogressive disease is defined as having 3 or fewer lesions of progression (sites can be local, distant, or both). Multiple mediastinal lesions will be counted as 1 lesion
Disqualifiers
Patients who rapidly progressed on the PACIFIC regimen (chemoradiotherapy [CRT] + durvalumab). This is defined as any progression on the first 3-month imaging scan after starting durvalumab post-CRT
Patients who were treated with anti-PD-(L)1 therapy other than durvalumab
Participation in another clinical study with an investigational product during the last 4 weeks
Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study. No other investigational therapy is permitted after durvalumab and start of this protocol
Trial design
Design model
Single group
Treatments tested in this trial
Carboplatin
Drug
Given IV
Durvalumab
Biological/Vaccine
Given IV
Gemcitabine
Drug
Given IV
Local Consolidation Therapy
Procedure/Surgery
Undergo LCT
Nab-paclitaxel
Drug
Given IV
Paclitaxel
Drug
Given IV
Pemetrexed
Drug
Given IV
Quality-of-Life Assessment
Other intervention
Complete questionnaire
Questionnaire Administration
Other intervention
Complete questionnaire
Treatment groups
51 Participants
are divided into 2 treatment groups
Group A: Cohort A (oligoprogressive)Experimental treatment 4 interventions
Group B: Cohort B (polyprogressive)Experimental treatment 9 interventions
Trial outcomes
Primary outcomes
1
Progression free survival (PFS)
The Kaplan-Meier product-limit estimate of the PFS function will be estimated and displayed for each treatment group. The median PFS time will be given with 95% confidence interval. Summaries of the number and percentage of patients experiencing a PFS event, and the type of event (Response Evaluation Criteria in Solid Tumors version 1.1 or death) will be provided. As comparative analysis, the one-sample log-rank test will be used to test difference in PFS between treatment and the historical control.
Time frame
From local consolidative therapy (LCT) initiation until progression or death, assessed up to 2 years
Secondary outcomes
1
Overall survival (OS)1
Will be estimated in each study cohort by Kaplan-Meier estimate. Summaries of the number and percentage of patients who have died, are still in survival follow-up, are lost to follow-up and have withdrawn consent will be provided along with median OS. Furthermore, one-sample log-rank test will be used to test difference in OS between treatment and historical control. Multivariate Cox proportional hazards model will be fitted to investigate the association between OS1/OS2 and other important prognostic variables such as age, histology, and gender.
Time frame
From diagnosis to death, assessed up to 2 years
2
OS2
Will be estimated in each study cohort by Kaplan-Meier estimate. Summaries of the number and percentage of patients who have died, are still in survival follow-up, are lost to follow-up and have withdrawn consent will be provided along with median OS. Furthermore, one-sample log-rank test will be used to test difference in OS between treatment and historical control. Multivariate Cox proportional hazards model will be fitted to investigate the association between OS1/OS2 and other important prognostic variables such as age, histology, and gender.
Time frame
From LCT initiation until death, assessed up to 2 years
3
Rate of intralobar progression
Will be determined by surveillance imaging. Will be assessed using Kaplan-Meier estimate.
Time frame
Up to 2 years
4
Rate of mediastinal progression
Will be determined by surveillance imaging. Will be assessed using Kaplan-Meier estimate.
Time frame
Up to 2 years
Other outcomes
Sponsors and contacts
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