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

NCT ID: NCT04485026

Last Updated: 2025-04-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-04
• Study Completion Date: 2024-05-09

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.

Conditions

Non Small Cell Lung Cancer; Oligoprogressive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Local consolidative radiation therapy

Intervention Type: 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.

Standard of Care - Control Arm

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

Group Type: ACTIVE_COMPARATOR

Standard of care radiation therapy

Intervention Type: 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

Interventions

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.

Intervention Type: RADIATION

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

Intervention Type: DRUG

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.
• 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).
• If EGFR and/or ALK status is unknown, the patient is eligible.

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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Farris, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Other Identifiers

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WFBCCC62420

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00068259

Identifier Type: -

Identifier Source: org_study_id