Clinical trial NCT01222572: Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer
Official title: Stereotactic Boost for Locally Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Lung Cancer
NSCLC
Keywords: radiation therapy
stereotactic radiotherapy
stereotactic boost
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
First posted: 2010-10-18
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this research study the investigators are looking for the highest dose of a stereotactic radiation boost that can be given safely. Because stereotactic radiation is so precise, the investigators are testing whether it can be used to increase the dose to the primary tumor without significantly increasing the side effects the participant experiences; the goal is to improve the likelihood of killing the tumor.

Detailed description: Primary Objectives Phase I: Determination of the MTD and dose-limiting toxicities of a stereotactic boost to chemoradiotherapy for stage II/III non-small cell lung cancer.

Phase II: Two-year local control rate

Secondary Objectives

* To evaluate the safety and tolerability of a stereotactic boost to chemoradiotherapy.
* To determine the 2-year overall survival.
* To determine the 2-year disease-free survival.
* To determine the 2-year regional control rate.
* To characterize the change in pulmonary function tests over the first 2 years after chemoradiotherapy.

Statistical Design The Phase I study followed a standard 3+3 dose escalation design. Three dose levels were evaluated. The DLT observation period was the 7-week chemoradiotherapy period and the subsequent 8-week recovery period.

To better study the toxicity at the MTD of the stereotactic boost, there was a 10 patient expansion cohort.The primary endpoint of the phase II portion of the study was two-year local failure rate of the protocol treatment. Local failure was defined as biopsy-proven recurrent disease, or if a biopsy was not attainable, by increasing FDG-avidity on PET-CT on 2 consecutive scans at least 1 month apart. Based on prior studies, a 2-year local failure rate of 15% would be worthy of further study, while a 2-year local failure rate of 35% would not justify further utilization of the treatment. With 32 eligible patients on this study, the treatment will be deemed promising if at least 25 patients are free of local failure at 2 years. Using this design, there was an 8% probability of declaring the treatment worthy of further study if the true 2-year local failure rate was 35%, and a 90% probability of declaring the treatment worthy of further study if the true 2-year local failure rate was 15% by using a one-sided one-sample exact binomial test.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed stage II or stage III non-small cell lung cancer, or stage IV non-small cell lung cancer that will be treated with curative intent
* Evaluated by a surgeon and deemed inoperable
* Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 10mm or greater with chest CT scan.
* No active malignancy within the past 5 years, except for non-melanoma skin cancers or carcinoma in situ of the cervix
* 18 years or older
* Life expectancy of greater then 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Normal organ and marrow function as outlined in the protocol
* Forced expiratory volume (FEV1) of 1 L or greater OR 50% or greater of predicted

Exclusion Criteria:

* Primary tumor size greater then 6cm
* Prior history of thoracic radiotherapy
* May not be receiving any other study agents
* History of pulmonary fibrosis
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin or etoposide
* Primary tumor \< 1.5 cm beyond hilar lymphadenopathy (if any) and 1.5 cm from proximal bronchial tree, defined as the trachea, right and left mainstem bronchus, and lobar bronchi until the 1st lobar segment
* Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or breast feeding women
* Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
* Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy
* Patients who are planned to receive the following medication: granulocyte colony-stimulating factor (G-CSF), bevacizumab, cetuximab, cyclosporine, anti-tumor necrosis factor agents, amifostine.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 7-week chemoradiotherapy period and the subsequent 8-week recovery period
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute/Brigham and Women's Hospital
name: Raymond H. Mak, MD
role: PRINCIPAL_INVESTIGATOR
References: