Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Hypofractionated Boost before Chemotherapy and Radiation Therapy in Treating Patients with Stage II or III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Protocol: OSU-14091

Full Title

A Phase II trial Combining Hypofractionated Radiation Boost with Conventionally-Fractionated Chemoradiation in Locally Advanced Non-Small Cell Lung Cancer Not Suitable for Surgery.

Purpose

This phase II trial studies how well giving a hypofractionated boost to the primary tumor before standard chemotherapy and radiation therapy works in treating patients with stage II or III non-small cell lung cancer that cannot be removed by surgery. Advances in radiation oncology have allowed better radiation targeting which may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and etoposide, 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. Radiation therapy uses high energy x-rays to kill tumor cells. Giving more precise and targeted radiosurgery before standard chemotherapy and radiation therapy may kill more tumor cells and prevent the cancer from coming back in the location in which it started.

Study Objective

PRIMARY OBJECTIVES:

I. To estimate the local control rate at 12 months after a combined regimen of stereotactic body radiation therapy (SBRT) (stereotactic radiosurgery) with conventionally-fractionated chemoradiation in unresectable or medically-inoperable non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To further establish safety and tolerability of this regimen.

II. To estimate the rates of regional, distant control as well as progression-free survival and overall survival.

III. To evaluate the objective response rate (ORR) to this regimen.

IV. To evaluate the response of tumors to stereotactic (high-dose) radiation using magnetic resonance tumor perfusion imaging modalities (magnetic resonance [MR]-dynamic contrast-enhanced [DCE]/perfusion weighted imaging [PWI], MR-diffusion, blood oxygenation level dependent [BOLD] sequences).

OUTLINE:

Patients will receive a hypofractionated boost to the primary tumor over 2 fractions (at least 40 hours apart) during week 1. Beginning week 2, patients receive cisplatin intravenously (IV) on days 8, 15, 36, and 43; and etoposide IV over 60 minutes on days 8-12 and 36-40. Patients also undergo 3-dimensional (D) conformal radiation therapy once daily (QD) 5 days a week for a total of 30 fractions. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Are you eligible?

Inclusion Criteria:

All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) =< grade 1 (except alopecia) at the time of enrollment

Absolute neutrophil count >= 1.5 x 10^9/L

Hemoglobin >= 9 g/dL

Platelets >= 100 x 10^9/L

Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5; unless using warfarin for therapeutic anti-coagulation

Albumin >= 2.5 g/dL

Total bilirubin =< 1.5 x upper limit of normal (ULN)

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

Creatinine =< 1.5 ULN AND

Calculated creatinine clearance >= 50 mL/min (calculated by the Cockcroft-Gault formula) or

24-hour urine creatinine clearance >= 50 mL/min

Non-small cell lung cancer (NSCLC), histologically and/or cytologically proven

Clinical American Joint Committee on Cancer (AJCC) stage (7th edition) IIA-IIIB NSCLC (T1-4N1-3M0)

Patients must be considered unresectable or medically-inoperable

Non-bulky lymphadenopathy =< 3 cm as defined by computed tomography (CT) largest axial diameter

Patients must have primary tumor =< 6 cm as defined by CT largest axial dimension

Within 4 weeks of registration: patients must have CT chest with IV contrast, fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)-CT scan (or CT abdomen/pelvis), and magnetic resonance imaging (MRI) brain with IV contrast (or CT head with contrast if contraindications to MRI); a non-contrast MRI chest or brain is permitted if patient has allergy to CT contrast or renal insufficiency

Within 8 weeks of registration: pulmonary function tests (PFTs) including forced expiratory volume in one second (FEV-1) and diffusing capacity of the lung for carbon monoxide (DLCO)

Within 2 weeks of registration: patients must have vital signs, history/physical examination, laboratory studies (complete blood count panel [CBCP] with differential, chemistries including liver function tests, creatinine clearance [CrCl] assessment, pregnancy test if needed)

If a pleural effusion is present and visible on both CT scan AND chest x-ray, the investigator should exclude malignant disease by pleurocentesis to confirm cytologically-negative pleural fluid; if fluid is exudative or cytologically positive for tumor cells, patient is excluded

Life expectancy of at least 12 weeks in the opinion of investigator

Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Patients must be a minimum of 3 weeks from thoracotomy (if performed) and well-healed before starting treatment

Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14 days of the first administration of study treatment; urine human gonadotropin (HCG) is an acceptable pregnancy assessment

Nursing women may participate only if nursing is discontinued

Women/men of reproductive potential must be counseled on contraception/abstinence while receiving the study treatment

Exclusion Criteria:

Patients with contralateral hilar involvement (greater than 1.5 cm on short axis or positive on PET scan, or biopsy-proven)

Documented or pathologically-proven metastatic disease

Presence of nodules considered neoplastic in the same lobe as the primary tumor (stage T3), unless the nodule can be encompassed in the stereotactic boost (gross tumor volume [GTV]boost) without exceeding a total GTVboost size of 6 cm as defined by CT largest axial dimension

Presence of nodules considered neoplastic in other ipsilateral lobes (stage T4) or contralateral lobes (M1a)

Patients with history of pneumonectomy

Prior cytotoxic chemotherapy or molecularly-targeted agents (e.g. erlotinib, crizotinib), unless > 2 years prior

Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix; patients with a previous malignancy without evidence of disease for >= 3 years will be allowed to enter the trial

History of active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis

History of previous radiation therapy to the chest which would result in overlapping fields

History of allergic reaction to cisplatin or etoposide

Uncontrolled neuropathy grade 2 or greater, regardless of cause

Subjects who are breast-feeding, or have a positive pregnancy test will be excluded from the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Significant pre-existing hearing loss, as defined by the patient or treating physician

Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator; this could include severe, active co-morbidities such as:

Uncontrolled cardiac disease (hypertension, unstable angina, myocardial infarction within last 6 months, uncontrolled congestive heart failure, cardiomyopathy with decreased ejection fraction)

Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration

Hepatic insufficiency resulting in jaundice and/or coagulation defects

Lung Cancers