Image-Guided, Intensity-Modulated Photon or Proton Beam Radiation Therapy in Treating Patients With Stage II-IIIB Non-small Cell Lung Cancer
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ClinicalTrials.gov Identifier: NCT01629498 |
Recruitment Status :
Recruiting
First Posted : June 27, 2012
Last Update Posted : June 18, 2021
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Condition or disease | Intervention/treatment | Phase |
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Recurrent Lung Non-Small Cell Carcinoma Stage II Non-Small Cell Lung Cancer AJCC v7 Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 Stage IIB Non-Small Cell Lung Carcinoma AJCC v7 Stage IIIA Non-Small Cell Lung Cancer AJCC v7 Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Radiation: Image Guided Radiation Therapy Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Radiation: Photon Beam Radiation Therapy Radiation: Proton Beam Radiation Therapy Other: Questionnaire Administration | Phase 1 Phase 2 |
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) of image-guided intensity-modulated photon (IMRT) and proton therapy (IMPT) both with simultaneous integrated boost (SIB) dose escalation to the SIBVi (internal SIB volume; defined as the gross tumor volume with consideration of respiratory motion plus setup uncertainty margin) for patients with stage II/IIIB non-small cell lung cancer (NSCLC) receiving concurrent standard chemotherapy and proton irradiation. (Phase I) II. Assess and compare survival free of grade III treatment related toxicity and local progression-free survival from day 1 of concurrent chemoradiation for stage II-IIIB NSCLC patients treated with image-guided robustly-optimized IMPT versus (vs.) IMRT, both delivered with simultaneous integrated boost (SIB). (Phase II)
SECONDARY OBJECTIVES:
I. Determine treatment-related acute and late toxicity. II. Correlate changes in standardized uptake values (SUV) on positron emission tomography (PET) and study endpoints (toxicity, tumor response, local control).
III. Correlate changes in peripheral blood biomarkers (genes, micro-ribonucleic acid [RNA], proteins) and the study endpoints.
IV. Estimate progression-free and overall survival. V. Document and compare symptom burden before starting chemoradiation, weekly during treatment, bi-weekly from end of treatment until first follow up, and at each follow-up visit thereafter by using the MD Anderson Symptom Inventory - Plus (MDASI-Plus) and European Quality of Life Instrument-5 dimensions (EQ-5D).
VI. Perform cost effectiveness between IMPT and IMRT both with SIB treatment. VII. Correlate imaged response, clinical response, blood biomarkers and symptom burdens to dose distribution patterns.
OUTLINE: This is a phase I, dose-escalation study followed by a randomized phase II study.
PHASE I: Patients undergo image-guided IMRT with SIB or IMPT with SIB once daily (QD) 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4-8 weeks, every 3-4 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 100 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase I/II Trial of Image-Guided, Intensity-Modulated Photon (IMRT) or Scanning Beam Proton Therapy (IMPT) Both With Simultaneous Integrated Boost (SIB) Dose Escalation to the Gross Tumor Volume (GTV) With Concurrent Chemotherapy for Stage II/III Non-Small Cell Lung Cancer (NSCLC) |
Actual Study Start Date : | September 17, 2012 |
Estimated Primary Completion Date : | September 30, 2022 |
Estimated Study Completion Date : | September 30, 2023 |

Arm | Intervention/treatment |
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Experimental: Arm I (image-guided IMRT)
Patients undergo image-guided IMRT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
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Radiation: Image Guided Radiation Therapy
Undergo image-guided IMRT
Other Names:
Radiation: Intensity-Modulated Radiation Therapy Undergo image-guided IMRT
Other Names:
Other: Laboratory Biomarker Analysis Optional correlative studies Radiation: Photon Beam Radiation Therapy Undergo image-guided IMRT Other: Questionnaire Administration Ancillary studies |
Experimental: Arm II (image-guided IMPT)
Patients undergo image-guided IMPT SIB QD 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
|
Radiation: Image Guided Radiation Therapy
Undergo image-guided IMPT
Other Names:
Radiation: Intensity-Modulated Radiation Therapy Undergo image-guided IMPT
Other Names:
Other: Laboratory Biomarker Analysis Optional correlative studies Radiation: Proton Beam Radiation Therapy Undergo image-guided IMPT
Other Names:
Other: Questionnaire Administration Ancillary studies |
- Maximum tolerated dose (MTD) for intensity-modulated photon therapy (IMRT) (Phase I) [ Time Frame: 90 days ]Will be defined as the highest simultaneous integrated boost volume (SIBV) dose that has posterior probability of dose-limiting toxicity (DLT) =< 30%. DLT are defined as Common Terminology Criteria for Adverse Events (CTCAE) 4.0 grade 3+ acute radiation toxicity, including esophagitis, pneumonitis, and skin reaction that are definitely, or probably related to radiation treatment. Toxicities will be tabulated by dose, severity, and relationship to radiation therapy.
- MTD for intensity-modulated proton therapy (IMPT) (Phase I) [ Time Frame: 90 days ]Will be defined as the highest SIBV dose that has posterior probability of DLT =< 30%. DLT are defined as CTCAE 4.0 grade 3+ acute radiation toxicity, including esophagitis, pneumonitis, and skin reaction that are definitely, or probably related to radiation treatment. Toxicities will be tabulated by dose, severity, and relationship to radiation therapy.
- Survival free of grade >= 3 toxicity (with a target of at least 75%) (Phase II) [ Time Frame: 6 months ]
- Local progression-free survival (75% at 6 months) d (Phase II) [ Time Frame: 6 months ]Will be defined as tumor recurrence or progression inside or at the boundary of the volume defined by the 60 Gy (relative biological effectiveness) isodose line. A Bayesian method will be applied.
- Time to local failure (Phase II) [ Time Frame: Up to 5 years ]The product-limit estimator of Kaplan and Meier will be used.
- Progression-free survival (Phase II) [ Time Frame: Up to 5 years ]The product-limit estimator of Kaplan and Meier will be used.
- Overall survival (Phase II) [ Time Frame: Up to 5 years ]The product-limit estimator of Kaplan and Meier will be used.
- Posterior probability that the DLT rate 90 days from day 1 of radiation therapy is more than 30% (Phase II) [ Time Frame: 90 days ]A 90% credible interval will be reported for this rate. Toxicities will be tabulated by severity and relationship to radiation therapy.
- Changes in selected biomarkers (Phase II) [ Time Frame: Baseline to up to 5 years ]Correlate changes in peripheral blood biomarkers (genes, ctDNA, microRNA, exosomes, proteins) and the study endpoints. Cox proportional hazards regression will be used to estimate the relationship between changes in selected biomarkers and time to local failure, progression-free survival, and overall survival.
- Change in symptom burden using European Quality of Life Five Dimension [EQ-5D]) (Phase II) Survey [ Time Frame: Up to 10 minutes ]Descriptive statistics and box plots will be used and will be measured by participants answers to the survey.
- Change in symptom burden using MD Anderson Symptom Inventory [MDASI]-Plus Survey [ Time Frame: Up to 10 minutes ]Descriptive statistics and box plots will be used and will be measured by participants answers to the survey.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Pathologically proven diagnosis of unresected stage II-IIIB, or recurrent after surgical resection or stereotactic body radiation therapy (SBRT) non-small cell lung cancer
- Suitability for concurrent chemoradiation therapy per treating physician's assessment
- Karnofsky performance status (KPS) score >= 70
- Weight loss < 15% in the 3 months before diagnosis
- Prior receipt of induction chemotherapy followed by referral for concurrent chemoradiation is allowed
- Adequate lung function indicated by forced expiratory volume at 1 second (FEV1) >= 1 L is required
- The primary tumor and/or regional lymph nodes must be evaluable radiographically
- The gross target volume (GTV) is suitable for motion management using 4 dimensional computed tomography (4D CT), internal target volume (ITV), or respiratory gating; in addition, the target coverage and normal tissue constraints must be met as specified in protocol accounting for the respiratory motion of anatomy as a whole (not just the tumor)
- No prior radiation to the mediastinal structures
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Total bilirubin =< 1.5 times the upper limit of normal (ULN)
- Alanine and aspartate transaminases (ALT and AST) =< 2.5 times the ULN (=< 5 x ULN for patients with liver involvement)
- Creatinine =< 1.5 times ULN
- Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of MD Anderson Cancer Center (MDACC)
Exclusion Criteria:
- Prior radiotherapy to any anatomic regions that would result in overlap of radiation dose distribution to critical structures (esophagus, heart, spinal cord, brachial plexus)
- T4 tumor with direct invasion of esophagus, spinal cord, major blood vessel, or heart
- Pregnancy
- Patients of childbearing potential must practice appropriate contraception
- Patient refusal

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01629498
Contact: Zhongxing Liao | 713-563-2300 | zliao@mdanderson.org |
United States, Texas | |
M D Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Zhongxing Liao 713-563-2300 zliao@mdanderson.org | |
Principal Investigator: Zhongxing Liao |
Principal Investigator: | Zhongxing Liao | M.D. Anderson Cancer Center |
Responsible Party: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT01629498 |
Other Study ID Numbers: |
2011-1058 NCI-2012-01224 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2011-1058 ( Other Identifier: M D Anderson Cancer Center ) P01CA021239 ( U.S. NIH Grant/Contract ) P30CA016672 ( U.S. NIH Grant/Contract ) U19CA021239 ( U.S. NIH Grant/Contract ) |
First Posted: | June 27, 2012 Key Record Dates |
Last Update Posted: | June 18, 2021 |
Last Verified: | June 2021 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Respiratory Tract Neoplasms |
Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms |