Local Consolidative Radiotherapy for Oligoprogressive in Non-small Cell Lung Carcinoma
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|ClinicalTrials.gov Identifier: NCT04485026|
Recruitment Status : Recruiting
First Posted : July 24, 2020
Last Update Posted : November 6, 2020
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer Oligoprogressive||Radiation: Local consolidative radiation therapy Drug: Standard of care radiation therapy||Phase 2|
Primary Objective: To compare overall survival (OS) from the time of the time of randomization between the treatment and control groups.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Estimated Study Start Date :||December 2020|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2025|
Experimental: 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.
Radiation: Local consolidative radiation therapy
All local consolidative radiation therapy should be delivered using hypofractionated local consolidative radiation therapy (>2 Gy per fraction). Exceptions may be approved on a case by case basis by the trial principal investigator. Three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic body radiotherapy (SBRT), stereotactic radiosurgery (SRS), and proton beam therapy (PBT) are all acceptable.
Active Comparator: Standard of Care - Control Arm
Second line systemic therapy is at the discretion of the treating medical oncologist.
Drug: Standard of care radiation therapy
Standard of care palliative radiotherapy to symptomatic lesions is permissible. The dose to symptomatic lesions should not exceed 30 Gy in 10 fractions. Brain metastases will be treated with standard of care CNS therapy throughout the study. This may include (but is not limited to) stereotactic radiosurgery, neurosurgical intervention, whole brain radiotherapy
- 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%).
- Time to Progression Between Both Arms [ Time Frame: 3 years ]Investigators will compare progression after second line of therapy between both arms first using the bivariate Kaplan-Meier method and then a multivariable Cox proportional hazards model age, ECOG status, number of progressive treated sites (1 vs 2-4), and PD-L1 status (>=50%; 1%-49%; < 1%). RECIST version 1.1 criteria will be used to assess for progression.
- Time to Second Line of Systemic Therapy or Palliative Care (Local Consolidative Radiation Therapy Arm Only) [ Time Frame: Up to 2 years after the completion of intervention ]The time to the second line systemic therapy or palliative care will be defined as the time from the completion of local consolidation therapy to the first day of cycle 1 of a systemic therapy the patient has not yet received OR the date of hospice enrollment, whichever is sooner. Patients experiencing neither of these events will be censored at last follow up visit. Estimated median time to second line therapy (or palliative care) and corresponding 95% confidence interval as well as estimated proportion (and corresponding 95% confidence interval) of the treatment group who have started second-line therapy (or palliative care) by key time points including 6 months, 1 year, and 2 years after the end of local consolidative therapy.
- Incidences of Toxicities [ Time Frame: Up to 3 years ]Toxicities will be evaluated per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicities between the two arms by comparing the proportions with grade 2 or higher, and grade 3 or higher, toxicities of any type at 3, 6, 12, 24 and 36 months following randomization using a chi-square test on the relevant 2x2 contingency table.
- Progression Free Survival [ Time Frame: Up to 5 years ]Progression free survival will be assessed by a modified RECIST version 1.1 criteria. If any individual target lesion meets RECIST v1.1 criteria - specifically an increase in the longest diameter (shortest diameter for lymph node lesions) of at least 20% and 5 mm absolute increase, the patient will be considered to have progression of disease. The criteria for determining pseudoprogression versus true progression and for mild progression while systemic therapy is held for the delivery of local consolidative radiation therapy in the treatment arm will be used for this outcome measure as well. Repeat oligoprogression will also be counted as progressive disease.
- Time to Next Progression Following Local Consolidative Radiation Therapy or Second Line Systemic Therapy [ Time Frame: Up to 3 years ]The pattern of next progression following local consolidation therapy (in treatment group) or second line systemic therapy (in control group) into one of three possible mutually exclusive and exhaustive categories: No progression, repeat oligoprogression or polyprogression, and will compare these patterns between the two groups using a chi-square analysis on the resulting 2x3 contingency table.
- Proportion of Local of Lesions Treated with Local Consolidative Radiation Therapy That Progress [ Time Frame: Up to 5 years ]Investigators will estimate proportion of lesions treated with local consolidative radiation therapy that experienced local progression (yes/no by study end) and construct a 95% confidence interval around this estimate.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04485026
|Contact: Study Nursefirstname.lastname@example.org|
|United States, Alabama|
|University of Alabama Birmingham Comprehensive Cancer Center||Not yet recruiting|
|Birmingham, Alabama, United States, 35233|
|Contact: Mike Soike, MD|
|Principal Investigator: Mike Soike, MD|
|United States, North Carolina|
|Wake Forest Baptist Comprehensive Cancer Center||Recruiting|
|Winston-Salem, North Carolina, United States, 27157|
|Contact: Study Nurse email@example.com|
|Principal Investigator: Michael Farris, MD|
|Principal Investigator:||Michael Farris, MD||Wake Forest University Health Sciences|