Clinical trial NCT01770418: A Phase I/II Study of Hypofractionated Proton Therapy for Stage II-III Non-Small Cell Lung Cancer
Official title: A Phase I/II Study of Hypofractionated Proton Therapy for Stage II-III Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lung Neoplasms
Keywords: Non Small Cell Lung Cancer
Cancer
Lung
Proton
Radiation
Lead sponsor: Proton Collaborative Group
Sponsor class: NETWORK
First posted: 2013-01-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed invasive non-small cell lung cancer within 12 weeks prior to study registration. OR Pathologically confirmed invasive non-small cell lung cancer within 6 months prior to study registration if the patient received induction chemotherapy.
* AJCC (American Joint Committee on Cancer) 7th Ed. clinical stage II-III.
* ECOG Performance status 0-1 within 8 weeks prior to study registration.
* Patient must give study-specific informed consent on an IRB-approved consent prior to any research-related procedures or study treatment.
* Patient must be at least 18 years old at the time of consent.
* Patient must complete all required tests in section 4.
* Lab results per the following within 4 weeks prior to study registration:

  * Absolute neutrophil count (ANC) \>1,800 cells/mm3.
  * Platelets \> = 100,000 cells/mm3.
  * Hemoglobin \> =10 g/dl. The use of transfusion or other intervention to achieve Hgb ≥10.0 g/dl is acceptable.
  * AST/SGOT and ALT/SGPT \< 2.5 x the institutional upper limit of normal (IULN).
* Post exploratory thoracotomy must be done \> 3 weeks prior to study registration or patient did not have post exploratory thoracotomy.
* PFT (pulmonary function test) with a FEV1 \> 0.75 liters/second within 16 weeks prior to study registration.
* Patients must be evaluated by a thoracic surgeon, pulmonologist or medical oncologist and deemed medically or surgically unacceptable for resection.

Exclusion Criteria:

* Evidence of distant metastasis (M1) involvement.
* Prior radiotherapy to thoracic area.
* Unintentional weight loss \>10% within 4 weeks prior to study registration.
* Pregnant and/or breast-feeding women, or patients (men and women) of child-producing potential not willing to use medically acceptable forms of contraception while on study treatment and for at least 12 months after study treatment. Pregnancy testing is not necessary for women who have had a hysterectomy or have not had a menstrual period for at least 24 consecutive months.

Primary outcomes:
measure: Phase I: Establish the maximum tolerated dose of radiotherapy in terms of Gy (RBE)/fraction using hypofractionated proton therapy concurrently with chemotherapy.
timeFrame: Weekly until completion of radiation treatment
measure: Phase II: Determine the percentage of patients that survive at least 12 months
timeFrame: At 12 months
Secondary outcomes:
measure: Assess acute and late adverse events of concurrent chemotherapy with hypofractionated proton therapy.
timeFrame: On average every 3 months for 5 years
measure: Analyze for disease control and overall survival.
timeFrame: At 2 years and 5 years
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida Proton Therapy Institute
state: Florida
city: Warrenville
country: United States
facility: Northwestern Medicine Chicago Proton Center
state: Illinois
city: Baltimore
country: United States
facility: Maryland Proton Treatment Center
state: Maryland
city: Somerset
country: United States
facility: Princeton ProCure Management LLC
state: New Jersey
city: Oklahoma City
country: United States
facility: Oklahoma Proton Center
state: Oklahoma
city: Hampton
country: United States
facility: Hampton University Proton Therapy Institute
state: Virginia
Study officials:
affiliation: Proton Collaborative Group
name: Brad Hoppe, MD
role: STUDY_CHAIR
References: