A Phase I/II Study of Hypofractionated Proton Therapy for Stage II-III Non-Small Cell Lung Cancer
The purpose of this research study is to compare the effects (good and bad) on subjects and their cancer using standard chemotherapy in combination with hypofractionated proton radiation therapy. Hypofractionation is a technique that delivers higher daily doses of radiation over a shorter period of time.
Radiation: Radiation Concurrent Chemotherapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Hypofractionated Proton Therapy for Stage II-III Non-Small Cell Lung Cancer|
- Phase I: Establish the maximum tolerated dose of radiotherapy in terms of Gy (RBE)/fraction using hypofractionated proton therapy concurrently with chemotherapy. [ Time Frame: Weekly until completion of radiation treatment ] [ Designated as safety issue: Yes ]This phase will have a minimum of 2 treated patients and we anticipate that the MTD will be located before a maximum of 28 patients are treated. The trial begins by treating 5 patients at 2.5 Gy (RBE)/fraction to a dose of 60 Gy (RBE).
- Phase II: Determine the percentage of patients that survive at least 12 months [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
- Assess acute and late adverse events of concurrent chemotherapy with hypofractionated proton therapy. [ Time Frame: On average every 3 months for 5 years ] [ Designated as safety issue: Yes ]
- Analyze for disease control and overall survival. [ Time Frame: At 2 years and 5 years ] [ Designated as safety issue: No ]
- To assess cost-effectiveness of this hypofractionated treatment course. [ Time Frame: At 2 and 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||March 2013|
|Estimated Primary Completion Date:||January 2038 (Final data collection date for primary outcome measure)|
|Experimental: Proton Radiotherapy with Chemotherapy||
Radiation: Radiation Concurrent Chemotherapy
RADIATION: Proton Radiotherapy Dose Level 1: 60 Gy (RBE) at 2.5 Gy(RBE)per fraction x 24 fractions
Dose Level 2: 60 Gy (RBE) at 3 Gy (RBE)per fraction x 20 fractions
Dose Level 3: 60.01 Gy (RBE) at 3.53 Gy (RBE)per fraction x 17 fractions
Dose Level 4: 60 Gy (RBE) at 4 Gy (RBE)per fraction x 15 fractions
Paclitaxel and Carboplatin or Cisplatin and Etoposide Paclitaxel at a dose of 45 mg/m2 and carboplatin at a dose of AUC 2 mg/min/ml(a total of 3-5 weekly doses) OR cisplatin 50mg/m2 days 1, 8, 29, and 36 and etoposide 50mg/m2 days 1-5, 29-33.
Adjuvant chemotherapy is optional but encouraged.
Conventional fractionated photon-based radiotherapy to 60-63 Gy at 1.8-2 Gy/fraction with concurrent chemotherapy remains the standard treatment practice in patients with stage III non-small cell lung carcinoma (NSCLC) with local control rates of approximately 50% and a median overall survival of just 18 months.Unfortunately, even the standard treatment has significant toxicity with approximately 40% of patients developing grade 3 or higher acute toxicities in the RTOG 9410 study.1 These outcomes are poor and more effective treatment regimens are needed.
Higher doses of radiation have been hypothesized to improve local control in patients with stage III NSCLC. This is expected to translate into better overall survival.Given the significant improvements in outcome in patients receiving hypofractionation for stage I NSCLC, perhaps similar gains could be achieved if hypofractionated radiotherapy could be safely delivered to stage II-III NSCLC with concurrent chemotherapy. Hypofractionated radiotherapy may offer improvement in local control compared with conventional fractionation that may translate into improved overall survival. Furthermore, hypofractionation will shorten the time interval during which patients are receiving less aggressive chemotherapy. Proton therapy is a highly conformal radiotherapy technique that takes advantage of the proton's characteristic Bragg Peak, resulting in significant reductions in the exit dose of the treatment beam. Thus, proton therapy can substantially reduce the dose to critical structures even compared with IMRT.
This study will investigate the safety and efficacy of delivering hypofractionated proton therapy with concurrent chemotherapy in patients with stage II-III NSCLC
|Contact: Angela Piper, MBA-PM||765-327-0344|
|United States, Florida|
|University of Florida Proton Therapy Institute||Recruiting|
|Jacksonville, Florida, United States, 32206|
|Contact: Judy Taylor-Holland 904-588-1401|
|Contact: Rochelle Carver 904-588-1475 email@example.com|
|Study Chair:||Brad Hoppe, MD||Proton Collaborative Group|