Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence

NCT00915005 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 2008-0133NCI-2011-010942P01CA021239-29A1
• Study Type: interventional
• Target: 275
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical research study is to learn if, compared with regular x-ray radiation, proton radiation reduces the risk of developing, treatment-related pneumonitis (TRP) or tumor recurrence (the tumor coming back in the irradiated area after treatment) in patients with lung cancer.

Conditions

Non-Small-Cell Lung Carcinoma

Keywords

Locally-advanced non-small-cell lung carcinoma; NSCLC; Lung Cancer; Image-Guided Adaptive Conformal Photon; Proton Therapy; Chemotherapy; Treatment Related Pneumonitis

Outcome Measures

Primary Outcomes (2)

• The Incidence and Time to Development of Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) Grade > 3 Treatment-related Pneumonitis (TRP)

  The Primary Objective is assess and compare the incidence and time to development of CTCAE v3.0 grade \> 3 TRP, among IMRT-Group 1 or PSPT-Group 2 using Bayesian randomization. TRP will be diagnosed clinically by the treating investigator. Any questions regarding the diagnosis or grade of TRP will be resolved by the Protocol PI or by his/her designee(s). The outcomes review committee will meet to discuss each and every patient reported to have developed symptomatic TRP. The final grading of TRP will be decided by the outcomes review committee. Diagnosis of TRP included receipt of radiation that included a certain volume of normal lung, radiographic changes that suggested inflammation consistent with the radiation dose distribution within 12 months after starting chemoradiation, and symptoms attributable to TRP. Final TRP outcomes also were reviewed and approved by independent external experts.

  From date of protocol registration until the date of first documented development of CTCAE v3.0 grade > 3 TRP or local failure, whichever occurs first, in both treatment groups, assessed up to 6 years.

• The Incidence and Time to Development of Local Failure (LF)

  The Primary Objective is assess and compare the incidence and time to development of local failure, among IMRT-Group 1 or PSPT-Group 2 using Bayesian randomization. Local failure was defined as treatment failure within the planning target volume plus a # 1-cm margin. Images used to report Local failure were registered with radiation dose distribution to accurately assess the location of the failure. Biopsy to confirm Local failure was strongly recommended (Data Supplement). An internal outcomes review committee reviewed each event to ensure objectivity and consistency in reporting Local failure. Final RP outcomes also were reviewed and approved by independent external experts. 1. Tumor recurrence after achieving complete response, 2. Residual tumor enlargement of 20% or more on CT according to RECIST criteria, 3. Recurrence of PET FDG Avidity after achieving complete metabolic response, 4. Increase in FDG avidity in residual tumor, 5. Pathologically proven recurrence

  From date of protocol registration until the date of first documented development of CTCAE v3.0 grade > 3 TRP or local failure, whichever occurs first, in both treatment groups, assessed up to 6 years.

Study Arms (4)

Group 1

EXPERIMENTAL

Group 1: Photon Therapy - 74 Gy 37 radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete. Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks. Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Radiation: Photon Therapy; Drug: Paclitaxel; Drug: Carboplatin

Group 2

EXPERIMENTAL

Group 2: Proton Therapy - 74 Gy in 2 CGE per fraction given 5 days a week for about 7 1/2 weeks. Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks. Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Radiation: Proton Therapy; Drug: Paclitaxel; Drug: Carboplatin

Group 3

EXPERIMENTAL

Group 3: Receives either photon or proton therapy, whichever participant's doctor decides is better, for for 6-7 1/2 weeks. Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks. Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Radiation: Photon Therapy; Radiation: Proton Therapy; Drug: Paclitaxel; Drug: Carboplatin

Group 4

EXPERIMENTAL

Photon Therapy - Highest practical dose (74 CGE, 66 CGE) radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete. Paclitaxel 50 mg/m2 by vein 1 time each week for 7 weeks. Carboplatin AUC 2 by vein 1 time each week for 7 weeks.

Radiation: Photon Therapy; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Photon Therapy RADIATION

Group 1: 74 Gy 37 radiation treatments, given 5 days a week for about 7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.

Group 1; Group 3; Group 4

Proton Therapy RADIATION

Group 2: 74 Gy in 2 CGE per fraction given 5 days a week for about 7 1/2 weeks. Group 3: 66 Gy with conventional fractionation given 5 days a week for about 6-7 1/2 weeks. Each daily treatment should take about 20-30 minutes to complete.

Group 2; Group 3

Paclitaxel DRUG

50 mg/m2 by vein 1 time each week for 7 weeks.

Also known as: Taxol

Group 1; Group 2; Group 3; Group 4

Carboplatin DRUG

AUC 2 by vein 1 time each week for 7 weeks.

Also known as: Paraplatin

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with solitary brain metastasis without sign of progression in the brain at the time of registration will be eligible for this trial if there is clinical indication for concurrent chemoradiation to the primary disease in the lung.
• Suitability for concurrent chemoradiation therapy per treating radiation oncologists or treating medical oncologist's: A) Karnofsky performance score of \>/= 70, or ECOG 0-1 B) Unintentional weight loss \</= 10% during the 3 months before study entry.
• Receipt of induction chemotherapy followed by referral for concurrent chemoradiation is allowed for this protocol.
• Measurable disease on chest x-ray, contrast-enhanced CT, or PET scan.
• Locoregional recurrence after surgical resection, if suitable for definitive concurrent chemoradiation is allowed for this protocol.
• Forced expiratory volume in the first second (FEV1) \>/= 1 liters.
• Fluorodeoxyglucose (FDG) -PET scan within 3 months before registration. The pretreatment (diagnostic) PET/CT should, whenever possible, be performed together with the 4-D CT simulation. PET images acquired either at the time of simulation or acquired separately should be registered with the planning CT to assist in tumor delineation.
• Standard pretreatment evaluations (as decided by treating radiation oncologist, medical oncologist, surgeons or pulmonologist), to include MRI or CT scan of the brain, contrast CT scan of the thorax and upper abdomen, Whole-body PET/CT, pulmonary function tests, lung and cardiac single proton emission computed tomography (SPECT), liver function tests (LFT), blood chemistry, renal function tests, and complete blood count.
• Age \>/= 18 years but \</= 85 years.
• A signed specific informed consent form before study entry.

You may not qualify if:

• Small cell histology.
• Prior thoracic radiotherapy to regions that would result in overlap of radiation therapy fields.
• Pregnancy (female patients of childbearing potential must practice appropriate contraception).
• Enrollment in a clinical trial that specifically excludes IGAPT treatment.
• Body weight exceeds the weight limit of the treatment couch.
• Oxygen dependent due to preexistent lung disease (COPD, emphysema, lung fibrosis).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77007, United States

Location

Related Publications (4)

• Koutroumpakis E, Xu T, Lopez-Mattei J, Pan T, Lu Y, Irizarry-Caro JA, Mohan R, Zhang X, Meng QH, Lin R, Xu T, Deswal A, Liao Z. Coronary artery calcium score on standard of care oncologic CT scans for the prediction of adverse cardiovascular events in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy. Front Cardiovasc Med. 2022 Dec 2;9:1071701. doi: 10.3389/fcvm.2022.1071701. eCollection 2022.

  PMID: 36531700 DERIVED

• Cella L, Monti S, Xu T, Liuzzi R, Stanzione A, Durante M, Mohan R, Liao Z, Palma G. Probing thoracic dose patterns associated to pericardial effusion and mortality in patients treated with photons and protons for locally advanced non-small-cell lung cancer. Radiother Oncol. 2021 Jul;160:148-158. doi: 10.1016/j.radonc.2021.04.025. Epub 2021 May 9.

  PMID: 33979653 DERIVED

• Gjyshi O, Xu T, Elhammali A, Boyce-Fappiano D, Chun SG, Gandhi S, Lee P, Chen AB, Lin SH, Chang JY, Tsao A, Gay CM, Zhu XR, Zhang X, Heymach JV, Fossella FV, Lu C, Nguyen QN, Liao Z. Toxicity and Survival After Intensity-Modulated Proton Therapy Versus Passive Scattering Proton Therapy for NSCLC. J Thorac Oncol. 2021 Feb;16(2):269-277. doi: 10.1016/j.jtho.2020.10.013. Epub 2020 Oct 22.

  PMID: 33198942 DERIVED

• Liao Z, Lee JJ, Komaki R, Gomez DR, O'Reilly MS, Fossella FV, Blumenschein GR Jr, Heymach JV, Vaporciyan AA, Swisher SG, Allen PK, Choi NC, DeLaney TF, Hahn SM, Cox JD, Lu CS, Mohan R. Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Jun 20;36(18):1813-1822. doi: 10.1200/JCO.2017.74.0720. Epub 2018 Jan 2.

  PMID: 29293386 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Proton Therapy; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Dr. Zhongxing Liao, MD/Professor, Radiation Oncology Department
• Organization: UT MD Anderson Cancer Center

zliao@mdanderson.org

(713) 563-2300

Study Officials

• Zhongxing Liao, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2009
• First Posted: June 5, 2009
• Study Start: June 1, 2009
• Primary Completion: February 24, 2020
• Study Completion: February 24, 2020
• Last Updated: May 26, 2020
• Results First Posted: May 26, 2020

Record last verified: 2020-05

Locations

US (2)