Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC

NCT03141359 | Active Not Recruiting Phase 2 Results DMC FDA Device

• 3 other identifiers: IRB0008138200021247LCI-LUN-NSC-SBRT-001
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer Stage II; Lung Cancer Stage III; Non Small Cell Lung Cancer

Keywords

Stereotactic body radiation; Chemoradiation; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants Progression Free and Surviving at 12 Months

  12-month progression free survival was determined for each subject as a binary variable indicating whether or not the subject was progression free and surviving at 12 months after study enrollment. Failure occurred if the subject progressed or died from any cause within 12 months of study enrollment. Disease progression was determined according to RECIST v1.1.

  From date of treatment start to date of progression or death, or censored at 12 months, whichever occurred first.

Secondary Outcomes (11)

• Progression Free Survival (PFS)

  From date of treatment start to date of progression or death, or censored as described; assessed for approximately 5 years

• Overall Survival (OS)

  From date of treatment start to date of death, or censored as described; assessed for approximately 5 years

• Radiologic Clinical Complete Response

  Approximately 3 months after last treatment of concurrent mediastinal chemoradiation (on average, SBRT plus chemoradiation treatment lasted 2 months from baseline)

• Number of Participants With an Objective Response

  From enrollment to best response while on study treatment; participants remained on study treatment (including SBRT, chemoradiation, and durvalumab) 4.5 months on average.

• Local Control at 12 and 24 Months

  From date of treatment start to date of progression of primary lesion or censored as described; assessed for approximately 2 years.]

Other Outcomes (7)

• Number of Participants With Grade 2 or Higher Radiation Pneumonitis

  From enrollment to 6 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 8 months).

• Number of Participants With Grade 3 or Higher Pulmonary Events

  Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months).

• Number of Participants With at Least One Serious Event

  Assessed for approximately 12 months after last treatment of concurrent mediastinal chemoradiation (on average, a total of 14 months).

Study Arms (1)

Single Arm

EXPERIMENTAL

SBRT + Concurrent Mediastinal Chemoradiation +/- Consolidation Chemotherapy/Adjuvant Immunotherapy

Radiation: SBRT; Drug: Carboplatin; Drug: Paclitaxel; Drug: cis Platinum; Drug: Etoposide; Radiation: IMRT; Drug: Durvalumab

Interventions

SBRT RADIATION

Primary tumor SBRT

Single Arm

Carboplatin DRUG

concurrent chemotherapy

Single Arm

Paclitaxel DRUG

concurrent chemotherapy

Single Arm

cis Platinum DRUG

concurrent chemotherapy

Single Arm

Etoposide DRUG

concurrent chemotherapy

Single Arm

IMRT RADIATION

mediastinal radiation

Single Arm

Durvalumab DRUG

adjuvant immunotherapy

Single Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Atrium Health Levine Cancer Institute: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Related Publications (1)

• Heinzerling JH, Mileham KF, Robinson MM, Symanowski JT, Induru RR, Brouse GM, Corso CD, Prabhu RS, Haggstrom DE, Moeller BJ, Bobo WE, Fasola CE, Thakkar VV, Pal SE, Gregory JM, Norek SL, Begic XJ, Kesarwala AH, Burri SH, Simone CB 2nd. Primary lung tumour stereotactic body radiotherapy followed by concurrent mediastinal chemoradiotherapy and adjuvant immunotherapy for locally advanced non-small-cell lung cancer: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2025 Jan;26(1):85-97. doi: 10.1016/S1470-2045(24)00573-4. Epub 2024 Nov 29.

  PMID: 39615497 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Paclitaxel; Cisplatin; Etoposide; durvalumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Chair of Biostatistics Department
• Organization: Atrium Health Levine Cancer

james.symanowski@atriumhealth.org

9804422371

Study Officials

• John H Heinzerling

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 5, 2017
• Study Start: May 12, 2017
• Primary Completion: July 12, 2023
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 5, 2026
• Results First Posted: August 29, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)