A Phase I/II Study of Hypofractionated Proton Therapy for Stage II-III Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT01770418
• Recruitment Status: Active, not recruiting
• First Posted: January 17, 2013
• Last Update Posted: April 4, 2023
• Sponsor: Proton Collaborative Group
• Information provided by (Responsible Party): Proton Collaborative Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lung Neoplasms	Radiation: Radiation with Concurrent Chemotherapy	Phase 1; Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: March 2013
• Estimated Primary Completion Date: January 2038

Arms and Interventions

Arm

Intervention/treatment

Experimental: Proton Radiotherapy with Chemotherapy

Radiation: Radiation with 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 CONCURRENT CHEMOTHERAPY: 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. For non squamous histology, Carboplatin AUC 5 on day 1 and Pemetrexed 500 mg/m2 on day 1 every 21 days OR Cisplatin 75 mg/m2 on day 1 and Pemetrexed 500 mg/m2 on day 1 every 21 days. Adjuvant chemotherapy is optional.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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).
2. Phase II: Determine the percentage of patients that survive at least 12 months [ Time Frame: At 12 months ]

Secondary Outcome Measures :

1. Assess acute and late adverse events of concurrent chemotherapy with hypofractionated proton therapy. [ Time Frame: On average every 3 months for 5 years ]
2. Analyze for disease control and overall survival. [ Time Frame: At 2 years and 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

University of Florida Proton Therapy Institute

Jacksonville, Florida, United States, 32206

United States, Illinois

Northwestern Medicine Chicago Proton Center

Warrenville, Illinois, United States, 60555

United States, Maryland

Maryland Proton Treatment Center

Baltimore, Maryland, United States, 21201

United States, New Jersey

Princeton ProCure Management LLC

Somerset, New Jersey, United States, 08873

United States, Oklahoma

Oklahoma Proton Center

Oklahoma City, Oklahoma, United States, 73142

United States, Virginia

Hampton University Proton Therapy Institute

Hampton, Virginia, United States, 23666

Sponsors and Collaborators

Proton Collaborative Group

Investigators

• Study Chair: Brad Hoppe, MD; Proton Collaborative Group

More Information

• Responsible Party: Proton Collaborative Group
• ClinicalTrials.gov Identifier: NCT01770418
• Other Study ID Numbers: LUN005-12
• First Posted: January 17, 2013
• Last Update Posted: April 4, 2023
• Last Verified: April 2023

Keywords provided by Proton Collaborative Group:

Non Small Cell Lung Cancer; Cancer; Lung; Proton; Radiation

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms