Local Consolidative Radiotherapy for Oligoprogressive in Non-small Cell Lung Carcinoma

NCT04485026 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: IRB00068259P30CA012197WFBCCC62420
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Non Small Cell Lung Cancer; Oligoprogressive

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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%).

  3 years

Secondary Outcomes (6)

• Time to Progression Between Both Arms

  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

• Incidences of Toxicities

  Up to 3 years

• Progression Free Survival

  Up to 5 years

• Time to Next Progression Following Local Consolidative Radiation Therapy or Second Line Systemic Therapy

  Up to 3 years

Study Arms (2)

Local Consolidative Radiation Therapy Arm

EXPERIMENTAL

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

Standard of Care - Control Arm

ACTIVE COMPARATOR

Second line systemic therapy is at the discretion of the treating medical oncologist.

Drug: Standard of care radiation therapy

Interventions

Local consolidative radiation therapy RADIATION

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.

Local Consolidative Radiation Therapy Arm

Standard of care radiation therapy DRUG

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

Standard of Care - Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age of 18 years or greater.
• ECOG Performance Status of 0-2.
• Negative serum or urine pregnancy test within 2 weeks of the date of enrollment
• for women of child-bearing potential.
• Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).

You may not qualify if:

• 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.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Michael Farris, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 24, 2020
• Study Start: November 4, 2020
• Primary Completion: May 9, 2024
• Study Completion: May 9, 2024
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share