A Randomized Phase II Study of Local Consolidative Radiotherapy Versus Standard of Care Second Line Systemic Therapy in Patients With Oligoprogressive NSCLC on Immune Checkpoint Inhibitors
Overview
- Phase
- Phase 2
- Intervention
- Local consolidative radiation therapy
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Wake Forest University Health Sciences
- Primary Endpoint
- Overall Survival
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
This is a randomized phase II study designed to evaluate the effect of local consolidative radiation therapy (LCT) to all sites of oligoprogressive disease in patients with metastatic non-small cell lung carcinoma who have progressed through first line systemic therapy containing an immune checkpoint inhibitor (ICI).
Detailed Description
Primary Objective: To compare overall survival (OS) from the time of the time of randomization between the treatment and control groups. Secondary Objective(s) * To compare the extra-CNS PFS2 (EC-PFS2), defined as the time to extracranial disease progression on second line systemic therapy or death from the first day of local consolidative radiation therapy (treatment group) or from the start of second line therapy (control group). * To evaluate time to initiation of second line systemic therapy or palliative care after completion of local consolidative therapy in the treatment group * To compare the toxicities in the treatment and control groups; * To compare overall progression free survival from the time of the first day of local consolidative radiation therapy for the treatment group and from the start of second line therapy for the control group * To compare the pattern of next progression on second line therapy in the treatment group vs the control group. * To evaluate local progression in lesions treated with local consolidative radiation therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed diagnosis of non-small cell lung cancer.
- •Have completed at least 4 cycles of a first line systemic therapy regimen for metastatic disease that includes a PD-1 axis targeted agent prior to progression. (Patients may be on maintenance/consolidation anti PD-1 axis therapy or have completed maintenance anti PD-1 axis therapy within the last 3 months at the time of progression).
- •Initial response of stable disease (SD), partial response (PR) or complete response (CR) in at least one lesion prior to progression as defined by RECIST v1.1 criteria.
- •Oligoprogressive disease in 4 or fewer lesions (Progression of the primary tumor and/or regional lymph nodes will be counted as one lesion)
- •CNS lesions will not count towards the 4 or fewer progressive lesions if they are all able to be treated with stereotactic radiosurgery.
- •Progression by RECIST v1.1 criteria or by PET/CT criteria will be considered progressive disease. Both are not required to determine progressive disease.
- •Progression for study entry will be defined as by a modified RECIST v1.1 criteria, including: Development of a new lesion; increase in the longest diameter (shortest diameter for lymph node lesions) of any individual lesion by 20% above nadir and a minimal increase of 5 mm.
- •In cases of PET/CT, the criteria for progression of PET/CT are: Any individual FDG avid lesion with an uptake greater than twice that of the surrounding tissue on the attenuation corrected image. Any individual FDG avid lesion with greater than 30% increase in 18F-FDG SUV peak, with greater than 0.8 SUV units increase in tumor SUV from the nadir or the pre-enrollment PET/CT in pattern typical of tumor and not of infection/treatment effect per the treating investigator. Visible increase in the extent of 18F-FDG uptake of any lesion by 20% in the longest diameter and an absolute increase of at least 5mm that is not consistent with treatment effect and/or infection per the treating investigator. No more than the following number of progressing lesions in any one organ (including any lesions previously treated with radiation therapy). Less than or equal to four (4) lung lesions (including primary and mediastinal lymph nodes as one lesion). Less than or equal to three (3) liver lesions. Less than or equal to three (3) cumulative vertebral lesions
- •At least one non-progressing lesion, which may not have undergone prior definitive local therapy.
- •All progressive lesions must be amenable to definitive radiation therapy as determined by the treating radiation oncologist.
Exclusion Criteria
- •Inability to safely treat all progressive lesions with definitive radiation therapy as determined by the treating radiation oncologist
- •Patients may not be receiving any other investigational anti-cancer agents.
- •Progressive disease in the CNS only.
- •Known targetable EGFR mutation or EML4-ALK fusion.
- •Progressive cutaneous metastases.
- •Progressive disease involving the esophagus, stomach, or intestines.
- •Malignant pleural or pericardial effusion at the time of oligoprogression.
- •Thoracentesis/thoracoscopic biopsy for a stable or asymptomatic pleural effusion is not required unless the effusion is hypermetabolic on PET/CT or if there are active pleural based metastatic lesions at the time of oligoprogression.
- •Effusions that are too small for thoracentesis/pericardiocentesis are considered resolved for the purposes of trial eligibility.
- •Pregnant women are excluded from this study because radiation therapy has known potential for teratogenic or abortifacient effects.
Arms & Interventions
Local Consolidative Radiation Therapy Arm
Definitive external beam radiation therapy will be delivered to all sites of progressive disease for all patients. The technique used to deliver radiation therapy will be determined by the treating radiation oncologist.
Intervention: Local consolidative radiation therapy
Standard of Care - Control Arm
Second line systemic therapy is at the discretion of the treating medical oncologist.
Intervention: Standard of care radiation therapy
Outcomes
Primary Outcomes
Overall Survival
Time Frame: 3 years
In each arm overall survival will be defined as the time from randomization to death from any cause. . Patients who are alive at the last follow up at the end of the study will be censored at the date of the last follow up appointment. A comparison of overall survival between the two groups will be made first using bivariate Kaplan-Meier method and then a multivariable Cox proportional hazards model. Participants who do not die during the course of observation will be right censored. Key covariates to be included in multivariable modeling include age, ECOG status, number of progressive treated sites (1 vs 2-4), and PD-L1 status (\>=50%; 1%-49%; \< 1%).
Secondary Outcomes
- Time to Progression Between Both Arms(3 years)
- Time to Next Progression Following Local Consolidative Radiation Therapy or Second Line Systemic Therapy(Up to 3 years)
- Incidences of Toxicities(Up to 3 years)
- Time to Second Line of Systemic Therapy or Palliative Care (Local Consolidative Radiation Therapy Arm Only)(Up to 2 years after the completion of intervention)
- Progression Free Survival(Up to 5 years)
- Proportion of Local of Lesions Treated with Local Consolidative Radiation Therapy That Progress(Up to 5 years)