Maintenance Chemotherapy with or without Local Consolidative Therapy in Treating Patients with Stage IV Non-small Cell Lung Cancer
- Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up.
- Women of childbearing potential and men who are sexually active should be willing and able to use medically acceptable forms of contraception during the trialtreatment on this study and for up to 180 days after completion of all treatment to prevent pregnancy or fathering a child.
- Pathologically proven diagnosis of NSCLC, with metastases (stage IV disease) present prior to registration; this includes patients newly diagnosed with metastatic disease or those initially diagnosed and treated for stage I-III NSCLC who ultimately develop metastases.
- Appropriate stage for study entry based on the following diagnostic workup: * History/physical examination by a radiation oncologist (and a surgeon if surgery is planned) within 30 days prior to registration * Imaging proof of limited metastatic disease and response to therapy/stable disease, by at least diagnostic quality computed tomography (CT) chest through the adrenals or positron emission tomography (PET)/CT, within 30 days prior to registration.
- Zubrod performance status 0, 1, or 2 within 30 days prior to registration.
- Aspartate transaminase (AST) and alanine transaminase (ALT) =< 2.5 x upper limit of normal (ULN) or =< 5 x ULN with metastatic liver disease within 14 days prior to registration.
- Total bilirubin =< 1.5 x ULN within 14 days prior to registration.
- Absolute neutrophil count (ANC) >= 500 cells/mm^3 within 14 days prior to registration.
- Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal within 14 days prior to registration
- Platelets >= 50,000 cells/mm^3 within 14 days prior to registration.
- For patients who will undergo resection of disease (if randomized to Arm 2 and dispositioned to receive surgery), adequate pre-surgical work-up for anticipated surgery, as defined by institutional guidelines
- Negative serum pregnancy test within one week prior to registration for females of childbearing potential.
- Patients must have received first-line/induction systemic therapy comprising of immunotherapy and/or platinum-based chemotherapy (a total of 4 cycles or courses), and achieved stable disease or a partial response.
- Prior systemic therapy as part of concurrent treatment approach for previously diagnosed stage III NSCLC, adjuvant therapy for stage III NSCLC, as adjuvant therapy for previously resected NSCLC, or for other previous cancers is permitted.
- Patients must have measurable disease at baseline and 3 or fewer discrete, extracranial metastatic disease sites that are technically amenable to stereotactic body radiation therapy (SBRT) or resection (at least one disease site must be amenable to radiation); some examples of what constitutes specific radiation treatment sites defining distinct metastatic disease sites are as follows: a) A lesion in each adrenal gland represents 2 of 3 sites of metastatic disease allowed to be treated on protocol; b) Similarly to NRG study RTOG 0631, disease in 2 contiguous vertebral bodies (with up to 6 cm of paraspinal extension) can represent one site of disease in the spine; non-contiguous lesions in vertebral bodies separated by one vertebral body free of disease should be viewed as 2 sites of treatment; and c) Two lesions in such close proximity to one another that treatment with one isocenter is more accurate and safer in the liver, lungs, or other similar anatomic locations should be viewed as one site of metastatic disease treatment.
- For de novo stage IV NSCLC patients (patients with metastatic disease at first presentation), primary disease must be treatable with local therapy in the form of SBRT or hypofractionated radiation. If the primary disease is found in the peripheral or central lung parenchyma without nodal disease, for instance, SBRT may be employed at the discretion of the treating institution. If primary disease is more advanced with involvement of the mediastinum (T4 tumor, N1-N3 disease, etc.), these volumes should be technically treatable with hypofractionated radiation; surgery should only be used for metastatic tumors that can be completely resected by lobectomy, segmentectomy, or wide wedge resection.
- If primary disease in the thoracic cavity was previously treated with local therapy in the form of surgery or radiation, any new local/regional disease recurrence should be technically treatable with SBRT or hypofractionated radiation after induction systemic therapy.
- Patients must be registered within 35 days of administration of the last dose of first-line/induction systemic therapy.
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.
- Prior radiotherapy for patients with brain metastases prior to enrollment is acceptable.
- Patients with brain metastases are eligible if these lesions have been previously treated and the patients have no clinical or radiographic evidence of progression within 30 days prior to enrollment.
- At least one site of metastatic disease or primary disease must be determined by radiation oncologist to be treatable with radiation.
- Subjects may receive palliative radiotherapy for symptomatic metastases prior to enrollment provided that there is at least one other non-irradiated lesion amenable to LCT at the time of enrollment.
- Clinical or radiologic evidence of new, untreated, and/or progressive brain metastases prior to registration after induction systemic therapy.
- Cutaneous metastasis of NSCLC.
- Metastatic disease invading the esophagus, stomach, intestines, or mesenteric lymph nodes if not a candidate for surgery for these lesions.
- Prior invasive malignancy (except non-melanomatous skin cancer, low or intermediate risk prostate cancer, or in situ carcinoma of breast, oral cavity, skin, or cervix) unless disease free for a minimum of one year.
- Metastases located within 3 cm of previously irradiated (< 3Gy per fraction) structures if not a candidate for surgery for these lesions and if: * Spinal cord previously irradiated to > 40 Gy * Brachial plexus previously irradiated to > 50 Gy * Small intestine, large intestine, or stomach previously irradiated to > 45 Gy * Brainstem previously irradiated to > 50 Gy * Lung previously irradiated with prior V20 Gy > 35%
- Patients receiving targeted therapy (non-cytotoxic, non-immunotherapy based systemic therapy) for NSCLC in the first-line setting. Such designations would include but not be limited to treatments targeting EGFR mutant positive or ALK positive NSCLC in the first-line setting.
- If a patient has progressed in previous areas of primary disease that received definitive doses of radiation, these patients would require re-irradiation in previous high dose anatomic areas and are not eligible for this study.
- Patients with malignant pleural effusions that do not resolve after first-line systemic therapy. Patients with pleural effusions that have become too small for thoracentesis at the time of registration would be permitted on study, indicating a significant response to first-line systemic therapy.
- Patients with more than 3 discrete locations of extra-cranial metastatic disease after first-line systemic therapy requiring more than 3 radiation/surgery plans to cover these distinct metastatic disease entities.
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 180 days after the completion of all treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding are also excluded.
- Participation in any investigational drug study (excluding non-oncology and/or symptom management studies) within 4 weeks prior to registration.
- Known human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol; this exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- Patients who received prior pembrolizumab, patients on chronic steroids or who have active autoimmune disease for which they received systemic treatment in the previous 2 years with corticosteroids, disease modifying agents, or immunosuppressive drugs; replacement therapy (thyroxine, insulin or physiological corticosteroid replacement for adrenal or pituitary insufficiency) is allowed; patients with active interstitial lung disease or who have a history of pneumonitis for which they had received glucocorticoids are not eligible.
- Prior bevacizumab therapy is excluded.
South San Francisco
Hilton Head Island
Salt Lake City
Fond Du Lac
I. To evaluate the impact of adding LCT (local consolidative therapy) to maintenance systemic therapy versus maintenance systemic therapy alone on progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC) with no evidence of progression and limited metastatic sites after first-line systemic therapy. (Phase II)
II. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on overall survival for patients with metastatic NSCLC with no evidence of progression and limited metastatic sites after first-line systemic therapy. (Phase III)
I. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on in-field local failure.
II. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on the time to development of new lesions.
III. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on toxicity.
IV. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance systemic therapy alone on duration of maintenance systemic therapy usage.
V. To evaluate the effect of adding LCT to systemic therapy in limited stage IV NSCLC on quality of life (QOL).
VI. To collect biospecimens and evaluate the correlation between clinical outcomes and circulating tumor deoxyribonucleic acid (DNA) (ctDNA).
OUTLINE: Patients are randomized into 1 of 2 arms.
ARM 1 (CHEMOTHERAPY ALONE): Patients may receive docetaxel intravenously (IV) over 60 minutes on day 1, or gemcitabine IV over 30 minutes on days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on day 1 alone or in combination with pembrolizumab IV over 30 minutes. Patients with >= 50% PD-L1 expression may receive pembrolizumab alone IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM 2 (SBRT AND CHEMOTHERAPY): Patients undergo LCT over 2-4 weeks. If LCT cannot be used to treat primary disease sites, patients also undergo intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3DCRT) over 3-5 weeks. Within 2 weeks after completion of radiation therapy, patients receive chemotherapy as in Arm 1. Patients may possibly undergo surgery.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, then annually thereafter.
Trial Phase Phase II/III
Trial Type Treatment
- Primary ID NRG-LU002
- Secondary IDs NCI-2016-00849
- Clinicaltrials.gov ID NCT03137771