The Synergistic Metastases Annihilation With Radiotherapy and Docetaxel (Taxotere) [SMART] Trial for Non-Small Cell Lung Cancer (NSCLC)

Study Overview
=================
Brief Summary
-----------------
Primary goal of the study is to assess the overall survival of the addition of hypofractionated image guided radiotherapy concurrently with Docetaxel and cisplatin. Survival will be assessed at 1 year from the date of study enrollment to date of death.

Official Title
-----------------
A Randomized Phase II Trial of Docetaxel, Cisplatin, and Hypofractionated Radiotherapy Versus Docetaxel and Cisplatin for Limited Volume Stage IV Non-small Cell Lung Cancer: The Synergistic Metastases Annihilation With Radiotherapy and Docetaxel (Taxotere) [SMART] Trial

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Docetaxel and cisplatin
* Radiation: Docetaxel and cisplatin Plus Hypofractionated Radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or older Life expectancy > 6 months Histologically or cytologically confirmed diagnosis of NSCLC Patients with AJCC stage IV cancer with distant metastases and without malignant pleural or pericardial effusion at diagnosis and before start of study Patients with pleural effusion that is transudative, cytologically negative, and non-bloody are eligible as long as they are stable and do not impair the ability to define tumor volumes. If a pleural effusion is too small for diagnostic thoracentesis, the patient will be eligible. Primary and regional nodal disease that is encompassable in a reasonable radiotherapy portal: Patients with 1-5 sites of disease and amenable to RT therapy as seen on standard imaging (CT, MRI, bone scan, PET scan) Unidimensionally measurable disease (based on RECIST) is desirable but not strictly required. Patients with brain metastases are allowed as long as they meet all other inclusion criteria. Brain metastases must be treated with whole brain radiotherapy and stereotactic radiosurgery or surgical resection followed by whole brain radiotherapy. ECOG performance status <2 No prior RT to currently involved tumor sites Baseline peripheral neuropathy < grade 1 Room air saturation (SaO2) > 90% Patients must have normal organ and marrow function Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. Signed Informed consent Inclusion of Women and Minorities RT: Patient must have a completed treatment plan approved by the protocol review team Exclusion Criteria: Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary heart disease will be at the discretion of the attending physician. Patients with significant atelectasis such that CT definition of the gross tumor volume (GTV) is difficult to determine. < 1000 cc of tumor free lung. Tumor volume and location which requires a lung volume-PTV >40% to receive >20 Gy (V20 <40%). Patients with exudative, bloody, or cytologically malignant effusions are not eligible. Pregnancy or breast feeding (Women of child-bearing potential are eligible, but must consent to using effective contraception during therapy and for at least 3 months after completing therapy) Patients must have no uncontrolled active infection other than that not curable without treatment of their cancer. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80. Patient may not be receiving any other investigational agents.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Chemotherapy only | Drug: Docetaxel and cisplatin<br>* Docetaxel 75 mg/m2 and cisplatin 75 mg/m2 IV repeated every 21 days for 2 additional cycles. For patients randomized to group 1, the chemotherapy is identical to that administered for the first 2 cycles<br>|
| Active Comparator: 2<br>Chemotherapy and hypofractionated image guided radiotherapy | Radiation: Docetaxel and cisplatin Plus Hypofractionated Radiotherapy<br>* Docetaxel 75 mg/m2 and cisplatin 75 mg/m2 IV for 2 cycles along with hypofractionated radiotherapy to all known sites of disease<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-Year Overall Survival | Overall survival is assessed at 1 year from the date of study enrollment to date of death. | Baseline to death from any cause, 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall PFS and CT Rate | Overall PFS and CT rate is assessed response with PET and CT. Toxicity of addition of high dose focused RT to systemic therapy.Late (>90 day) radiotherapy toxicity will be assessed with RTOG/EORTC late RT toxicity guidelines | >90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NSCLC, Metastatic Stage IV NSCLC, Limited Volume Stage IV Non-small Cell Lung Cancer