Clinical trial NCT03141359: Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC
Official title: LCI-LUN-NSC-SBRT-001: Phase II Prospective Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation and Adjuvant Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lung Cancer Stage II
Lung Cancer Stage III
Non Small Cell Lung Cancer
Keywords: Stereotactic body radiation
Chemoradiation
Immunotherapy
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Atrium Health Levine Cancer Institute
name: AstraZeneca
First posted: 2017-05-05
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, single-stage Phase II study designed to evaluate the 1-year PFS rate in subjects with locally-advanced NSCLC (stage II/III) and treated with Stereotactic Body Radiation Therapy (SBRT) followed by concurrent mediastinal chemoradiation with or without consolidation chemotherapy. A total of 60 subjects will be enrolled to this study over a 4 year accrual period.

Detailed description: This study's primary objective is to assess the efficacy of a treatment regimen involving Stereotactic Body Radiation Therapy (SBRT) delivered to the primary tumor followed by concurrent mediastinal chemoradiation by evaluating the proportion of subjects with locally-advanced non-small cell lung cancer (NSCLC) stage II/III who are alive and progression free at 12 months, and to compare to relevant historical controls. Additionally, the treatment regimen will be evaluated based on progression free survival, overall survival, radiologic clinical complete response rate following completion of therapy, objective response rate as defined by RECIST v 1.1, local and locoregional control, patterns of failure, and quality of life. Safety objectives include the rate of grade 2+ radiation pneumonitis and grade 3+ pulmonary events. Exploratory objectives include differential expression of cytokines and chemokines associated with radiation therapy will be determined.

Eligibility criteria: Inclusion Criteria

Subjects must meet all the following criteria:

* Histologic or cytologic documentation of NSCLC (all histologies allowed)
* Stage II or III disease (AJCC 7th Edition) based on imaging as required during screening: Stage II disease includes only subjects with medically inoperable N1 disease otherwise meeting eligibility criteria. Primary tumor ≤ 7 cm
* Subjects with non-malignant pleural effusion identified on CT scan are eligible provided the effusion is not known or demonstrated to be an exudative effusion. If a pleural effusion is present, the following criteria must be met to exclude malignant involvement: A pleuracentesis is required if pleural fluid is present and visible on both CT scan and chest x-ray. Pleural fluid cytology must be negative for malignancy. Effusions that are minimal and too small for pleuracentesis as determined by the investigator will be eligible for enrollment.
* FEV1 ≥ 1.0 Liter or ≥ 40% predicted with or without bronchodilator within six months prior to initiation of study treatment. Subjects who meet the criterion without O2, but who need acute (started within 10 days prior to enrollment) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable.
* Age ≥18 years.
* ECOG performance status ≤ 2
* Subjects must have normal organ and marrow function as defined: Leukocytes ≥4,000/mcL; Absolute neutrophil count ≥1,500/mcL; Platelets ≥100,000/mcL; Total bilirubin ≤1.5 times the upper limit of normal; Creatinine clearance ≥25 mL/min/1.73 m2
* Negative serum or urine pregnancy test prior to enrollment for women of childbearing age and potential.
* The effects of radiation on the developing human fetus are not well described. For this reason, women of child-bearing potential and non-sterilized men who are sexually active with a woman of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Must be considered a candidate for durvalumab, per the treating investigator
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

Subjects must not meet any of the following criteria.

* Subjects who have had prior systemic therapy for lung cancer
* Subjects who have had prior radiation to the region of the chest that would result in overlap of radiation therapy fields and determined by the treating physician to impede the treatment of the study malignancy.
* Subjects who are actively being treated on any other interventional research study.
* Prior invasive malignancy unless disease free for a minimum of 3 years from enrollment. However, non-melanoma skin cancer, low risk prostate cancer, well differentiated thyroid cancers, in situ carcinomas of the breast, oral cavity, cervix, and other organs, and tumors that are not thought to impact the life expectancy of the subject according to the treating investigator is permissible.
* Centrally located primary tumor \< 2 cm from involved nodal disease which would result in significant overlap of radiation dose. Centrally located is defined as within or touching the zone of the proximal bronchial tree, which is a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi).

Primary outcomes:
measure: Number of Participants Progression Free and Surviving at 12 Months
timeFrame: From date of treatment start to date of progression or death, or censored at 12 months, whichever occurred first.
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From date of treatment start to date of progression or death, or censored as described; assessed for approximately 5 years
measure: Overall Survival (OS)
timeFrame: From date of treatment start to date of death, or censored as described; assessed for approximately 5 years
measure: Radiologic Clinical Complete Response
timeFrame: Approximately 3 months after last treatment of concurrent mediastinal chemoradiation (on average, SBRT plus chemoradiation treatment lasted 2 months from baseline)
measure: Number of Participants With an Objective Response
timeFrame: From enrollment to best response while on study treatment; participants remained on study treatment (including SBRT, chemoradiation, and durvalumab) 4.5 months on average.
measure: Local Control at 12 and 24 Months
timeFrame: From date of treatment start to date of progression of primary lesion or censored as described; assessed for approximately 2 years.]
measure: Regional Control at 12 and 24 Months
timeFrame: From date of treatment start to date of progression of regional lesions or censored as described; assessed for approximately 2 years.
measure: Locoregional Control at 12 and 24 Months
timeFrame: From date of treatment start to date of progression of primary or regional lesions or censored as described; assessed for approximately 2 years.
measure: Distant Control at 12 and 24 Months
timeFrame: From date of treatment start to date of metastatic progression or censored as described; assessed for approximately 2 years
measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Score
timeFrame: baseline (pre-SBRT), post-SBRT/pre-chemoradiation, and 1, 3, 6, and 12 months after the last treatment of chemoradiation (on average, SBRT plus chemoradiation treatment lasted 2 months from baseline)
measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Lung Cancer (EORTC QLQ-LC13) Symptom Scores
timeFrame: baseline (pre-SBRT), post-SBRT/pre-chemoradiation, and 1, 3, 6, and 12 months after the last treatment of chemoradiation (on average, SBRT plus chemoradiation treatment lasted 2 months from baseline)
measure: MD Anderson Symptom Inventory - Lung Cancer (MDASI-LC) Total Symptom + Interference Score
timeFrame: baseline (pre-SBRT), post-SBRT/pre-chemoradiation, and 1, 3, 6, and 12 months after the last treatment of chemoradiation (on average, SBRT plus chemoradiation treatment lasted 2 months from baseline)
Other outcomes:
measure: Number of Participants With Grade 2 or Higher Radiation Pneumonitis
timeFrame: From enrollment to 6 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 8 months).
measure: Number of Participants With Grade 3 or Higher Pulmonary Events
timeFrame: Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months).
measure: Number of Participants With at Least One Serious Event
timeFrame: Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months).
measure: Number of Participants With at Least One Treatment Emergent Adverse Event
timeFrame: Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months).
measure: Number of Participants With at Least One Grade 3 or Higher Treatment Emergent Adverse Event
timeFrame: Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months).
measure: Number of Participants Who Discontinued Study Treatment Due to Adverse Events
timeFrame: Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months)
measure: Number of Participants Who Received Durvalumab
timeFrame: Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months).
Locations:
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: John H Heinzerling
role: PRINCIPAL_INVESTIGATOR
References: