Stereotactic Body Radiation Therapy and Chemotherapy in Treating Patients with Stage IIA-IIIA Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Status: Active

Description

This phase I trial studies the side effects and best dose of stereotactic body radiation therapy when given together with chemotherapy in treating patients with stage IIA-IIIA non-small cell lung cancer that cannot be removed by surgery. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Drugs used in chemotherapy, such as pemetrexed disodium, cisplatin, carboplatin, and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving stereotactic body radiation therapy with chemotherapy may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed non-small cell lung cancer
  • Medically or technically inoperable as per thoracic surgeon or patient's preference not to undergo surgical resection
  • 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 principal investigator [PI] if all normal tissue guidelines can be met)
  • Cohort A: Eligible for chemotherapy
  • Cohort A: Karnofsky performance status >= 70%
  • Cohort A: Men and women of childbearing potential must be willing to use effective contraception while on treatment and for at least 3 months thereafter
  • Cohort A: Calculated creatinine clearance >= 40 mL/min for patients receiving pemetrexed (by Cockcroft-Gault)
  • Cohort A: Calculated creatinine clearance >= 30 mL/min for patients receiving gemcitabine or paclitaxel (by Cockcroft-Gault)
  • Cohort A: Total bilirubin less than 1.5 x upper limit of normal (ULN) (unless known Gilbert's disease)
  • Cohort A: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 x ULN
  • Cohort A: Absolute neutrophil count greater than 1500/mm^3
  • Cohort A: Platelet count greater than 100,000/mm^3
  • 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

  • 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 positron emission tomography (PET)/endobronchial ultrasound-fine needle aspiration (EBUS-FNA)/mediastinoscopy (any N2 disease that is more than just minimal single station involvement is excluded)
  • Direct tumor extension into aorta or pulmonary artery
  • Chronic corticosteroid use equivalent to >= prednisone 10 mg daily
  • Prior treatment with a CD137 agonist, ipilimumab, or the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, or programmed death-1 (PD-1)/programmed cell death 1 ligand 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 ** Pacemakers and defibrillators are excluded ** Stents etc. will be evaluated according to Memorial Sloan Kettering Cancer Center (MSKCC) policy * Unmanageable claustrophobia * High risk for nephrogenic systemic fibrosis

Locations & Contacts

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Andreas Rimner
Phone: 212-639-6025
Email: rimnera@mskcc.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of stereotactic body radiation therapy (SBRT) with sequential chemotherapy for locally-advanced non-small cell lung cancer (NSCLC) without mediastinal lymph node involvement. (Cohort A)

SECONDARY OBJECTIVES:

I. Assess >= grade 4 or persistent grade >= 3 late toxicities (>= 3 months post SBRT) including late cough, dyspnea, esophageal strictures, brachial plexopathy, and chest wall pain. (Cohort A)

II. Perform exploratory immunology studies before and after SBRT on the peripheral blood levels of

IIa. T-cells: activation and memory markers, e.g. activated cluster of differentiation (CD)8+ T-cells, activated ICOS-high CD4+ T-cells, and T regulatory (reg) cells (CD4 + FOXP3+).

IIb. Myeloid-derived suppressor cells, e.g. CD14+ human leukocyte antigen (HLA)-DR low.

IIc. Serology assay: to identify cancer-testis antigen-specific antibody response against e.g. NY-ESO-1, LAGE, MAGE1 and MAGE3. (Cohorts A and B)

III. Assess early intratumoral vascular changes to high-dose SBRT as measured by functional magnetic resonance imaging (MRI). (Cohorts A and B)

IV. Assess local progression-free survival, locoregional control, distant-metastasis-free survival and overall survival. (Cohort A)

OUTLINE: This is a dose-escalation study of SBRT. Patients are assigned to 1 of 2 cohorts.

COHORT A:

SBRT: Patients undergo SBRT every other day (3-5 fractions total). Patients are then assigned to 1 of 3 chemotherapy regimens.

PEMETREXED + CISPLATIN OR CARBOPLATIN: Beginning 6-8 weeks after SBRT, patients with non-squamous NSCLC receive pemetrexed disodium intravenously (IV) over 10 minutes and cisplatin IV over 1 hour or carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

GEMCITABINE + CISPLATIN OR CARBOPLATIN: Beginning 6-8 weeks after SBRT, patients with squamous NSCLC receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 1 hour or carboplatin IV over 30 minutes on day 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

PACLITAXEL + CARBOPLATIN: Beginning 6-8 weeks after SBRT, patients with either histology, with a medical contraindication to the assigned regimen of pemetrexed or gemcitabine, receive paclitaxel IV over 3 hours and carboplatin over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients undergo SBRT every other day (=< 8 fractions total).

After completion of study treatment, patients are followed up every 3 months for 1 year.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Andreas Rimner

Trial IDs

Primary ID 13-113
Secondary IDs NCI-2013-01323
Clinicaltrials.gov ID NCT01899989