Stereotactic Body Radiation Therapy for Inoperable Locally-advanced Non-small Cell Lung Cancer

The purpose of this study is to determine if the use of exploratory immunologic biomarkers, functional MRI images can serve as early predictors for response of NSCLC. It also will provide important information on the perceived side effects from a patient perspective. Patients may participate if they have tumors ≥3 cm without lymph node involvement (for which chemotherapy is not part of the standard of care). Patients will only receive stereotactic body radiation therapy (SBRT) per standard dose guidelines.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: cisplatin or carboplatin-based

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Cancer Center at Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States
      • Memorial Sloan Kettering at Mercy Medical Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All patients:

• Histologically confirmed non-small cell lung cancer
• Medically or technically inoperable as per thoracic surgeon or patient's preference not to undergo surgical resection
• Age ≥ 18 years
• Women of childbearing potential must have a negative blood pregnancy test
• Ability to provide written informed consent

Cohort A:

• Stage IIA-IIIA (TanyN1M0 or T2b-4N0M0) Selected patients with single station N2 nodal involvement in close proximity to the primary tumor target may be considered eligible at the discretion of the PI if all normal tissue guidelines can be met
• Eligible for chemo-therapy
• Karnofsky Performance Status ≥70%
• Men and women of childbearing potential must be willing to use effective contraception while on treatment and for at least 3 months thereafter

• Patients must show adequate organ function as defined by:

  • Calculated creatinine clearance ≥40 mL/min for patients receiving pemetrexed (by Cockcroft-Gault)
  • Calculated creatinine clearance ≥30 mL/min for patients receiving gemcitabine or paclitaxel (by Cockcroft-Gault) Total bilirubin less than 1.5 x ULN (unless known Gilbert's disease)
  • AST and ALT less than 3 x ULN
  • Absolute neutrophil count greater than 1500/mm3
  • Platelet count greater than 100,000/mm3

Cohort B:

• T2a-4N0M0 who are not candidates for cohort A or who will not be treated with chemotherapy (due to patient preference or at the recommendation of the treating physician).

Exclusion Criteria:

All patients:

• Prior radiation therapy to the lungs
• Prior surgery or chemotherapy for this presentation of lung cancer (history of prior lung cancer that has been treated and deemed inactive by the clinician is acceptable. Recurrent tumors may be treated on protocol as long as SBRT will be the definitive treatment.)
• N2-3 lymph node involvement based on PET/EBUS-FNA/mediastinoscopy (Any N2 disease that is more than just minimal single station involvement is excluded)
• Direct tumor extension into including aorta or pulmonary artery
• Chronic corticosteroid use equivalent to ≥ prednisone 10 mg daily

Prior treatment with a CD137 agonist, ipilimumab, or the CTLA-4 inhibitor, or PD-1/PDL-1 inhibitor

• Unstable congestive heart failure

Cohort A:

• Continuous oxygen use

Patients meeting the following exclusion criteria will be excluded from the functional MRI portion only:

• Metallic implant,exclusions will be determined per institutional policies
• Pacemaker and defibrillators are excluded
• Stents etc. will be evaluated according to MSKCC policy
• Unmanageable claustrophobia
• High risk for nephrogenic systemic fibrosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A) >5cm,Chemo eligible (closed to accrual); Patients will receive five fractions of either 8, 10, or 12 Gy to the gross tumor only. Following SBRT patients will be evaluated by their medical oncologist for consideration of adjuvant chemotherapy, starting 6-8 weeks post-RT. All patients will be followed for one year. Patients will be assessed for toxicity by their radiation oncologist at 4 to 6 weeks post-RT and during chemotherapy by their medical oncologist. Follow up after completion of all treatment will consist of CT chest scans at 6 and 12 months post-SBRT and toxicity assessments every 3 months from the end of SBRT for one year.	Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: cisplatin or carboplatin-based; Standard chemotherapy with a histology-selected cisplatin or carboplatin-based doublet will be administered intravenously as adjuvant therapy. Gemcitabine will be used for squamous cell carcinomas and pemetrexed will be used for non-squamous non-small cell lung cancer. Cisplatin or carboplatin will be used in combination with the histology-selected agent. The choice of cisplatin or carboplatin will be at the discretion of the treating medical oncologist.
Experimental: B) 3-5cm OR Chemo ineligible; Using intensity-modulated radiation therapy (IMRT) or volumetric arc therapy (VMAT), the choice of which is determined by the radiation oncologist, patients will be treated in < 5 fractions every other day. The total treatment dose will be between 45 and 54 Gy in < 5 fractions per standard of care. All patients will be followed for one year. Patients will be assessed for toxicity by their radiation oncologist at 4 to 6 weeks post-RT and during chemotherapy at the discretion of their medical oncologist. Follow up after completion of all treatment will consist of CT chest scans at 6 and 12 months post-SBRT and toxicity assessments every 3 months from the end of SBRT for one year. FDG PET/CT scans and Pulmonary Function Tests (PFTs) will be obtained at 3 months and 9 months after SBRT.	Radiation: Stereotactic Body Radiation Therapy (SBRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum tolerated dose (Cohort A)	standard 3+3 dose-escalation scheme	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
≥ grade 4 or persistent ≥ grade 3 late toxicities (Cohorts A & B)	All patients will be assessed for toxicities according to CTCAE v 4.0 at least once during SBRT.	≥3 months post SBRT
overall survival (Cohorts A & B)	Response and progression will be evaluated per standard of care for radiographic progression on CT scans.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Abraham Wu, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: July 5, 2013
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 11, 2013
• First Posted (Estimated): July 16, 2013

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Chemotherapy; Stereotactic Body Radiation Therapy (SBRT); 13-113
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: 13-113