Positron Emission Tomography and Computed Tomography in Guiding Radiation Therapy for Stage III Non-small Cell Lung Cancer

NCT01507428 | Completed Phase 2 Results

• 6 other identifiers: NCI-2012-00107CDR0000721619ACRIN-6697RTOG-1106U10CA180868U10CA021661
• Study Type: interventional
• Target: 138
• Locations: 2 countries
• Sites: 31

Brief Summary

This randomized phase II trial studies how well positron emission tomography (PET)/computed tomography (CT)-guided radiation therapy works compared to standard radiation therapy in treating patients with stage III non-small cell lung cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Using imaging procedures, such as PET and CT scans, to guide the radiation therapy, may help doctors deliver higher doses directly to the tumor and cause less damage to healthy tissue.

Conditions

Stage III Lung Non-Small Cell Cancer AJCC v7; Stage IIIA Lung Non-Small Cell Cancer AJCC v7; Stage IIIB Lung Non-Small Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Alive Without Local-regional Progression [Local-regional Progression-free (LRPF) Survival] at Two Years (NRG)

  LRPF survival is defined as survival without local-regional progression (LRP) as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria with integration of 8F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and reviewed centrally based on submitted CT scans. LRP is defined as any of the following: * ≥ 20% increase in any of the target lesions (primary and nodal disease), * ≥ 20% increase in the peak SUV of target lesions, * appearance of one or more new lesions within previously irradiated regions. LRPF-free survival time is defined as time from registration to the date of first local-regional progression, distant recurrence (censored), death without documented LRP (censored), or death. LRPF survival rates are estimated using the Kaplan-Meier method.

  Randomization to 2 years

• Relative Change in SUVpeak From the Baseline to the During-treatment Fludeoxyglucose F 18 (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) to LRPF With a 2-year Follow up. (ECOG-ACRIN)

  To determine whether the relative change in SUVpeak (from the baseline to the during-treatment FDG-PET/CT) can predict the LRPF with a 2-year follow up. Relative ΔSUVpeak = (Mid-treatment SUVpeak - baseline SUVpeak)/baseline SUVpeak x 100 LRPF was determined from Randomization up to 2 years

  Baseline to during-treatment (approximately between fractions 18-19) Randomization to 2 years

Secondary Outcomes (25)

• Percentage of Participants With Local-regional Progression (NRG)

  From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.

• Percentage of Participants Alive (Overall Survival) (NRG)

  From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.

• Percentage of Participants Alive Without Progression (Progression-free Survival) (NRG)

  From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.

• Percentage of Participants With Death Due to Lung Cancer (NRG)

  From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years. Two-year rates reported here.

• Percentage of Participants With Grade 3+ Radiation-induced Lung Toxicity [RILT] at Any Time (NRG)

  From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years.

Other Outcomes (2)

• Quantify Relationship Between Biomarkers and Grade 2+ Radiation-induced Lung Toxicity [RILT] (NRG)

  Randomization to last follow-up.

• Quantify Relationship Between Biomarkers and Two-year Local-regional Progression-free (LRPF) Survival (NRG)

  From randomization to last follow-up: weekly during treatment, then 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months after end of protocol treatment, then annually. Maximum follow-up at time of reporting was 7.3 years.

Study Arms (2)

Arm I (standard chemoradiotherapy)

ACTIVE COMPARATOR

Patients undergo radiotherapy QD 5 days a week for 30 fractions. Patients also receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes once weekly for 6 weeks. Patients undergo FDG-PET/CT imaging between fractions 18 and 19.

Drug: 18F-Fluoromisonidazole; Drug: Carboplatin; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Drug: Fludeoxyglucose F-18; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Procedure: Positron Emission Tomography

Arm II (experimental chemoradiotherapy)

EXPERIMENTAL

Patients undergo an individualized dose of image-guided radiotherapy QD 5 days a week for 30 fractions and undergo 18 F FDG-PET/CT between fractions 18 and 19. Based on the scan results, patients undergo individualized adaptive radiotherapy for the final 9 fractions. Patients also receive paclitaxel and carboplatin as in Arm I.

Drug: 18F-Fluoromisonidazole; Drug: Carboplatin; Procedure: Computed Tomography; Drug: Fludeoxyglucose F-18; Radiation: Image-Guided Adaptive Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Procedure: Positron Emission Tomography

Interventions

18F-Fluoromisonidazole DRUG

Undergo FMISO PET/CT (Correlative studies)

Also known as: 18F-MISO, 18F-Misonidazole, FLUOROMISONIDAZOLE F-18, FMISO

Arm I (standard chemoradiotherapy); Arm II (experimental chemoradiotherapy)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (standard chemoradiotherapy); Arm II (experimental chemoradiotherapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (standard chemoradiotherapy); Arm II (experimental chemoradiotherapy)

Computed Tomography PROCEDURE

Undergo FDG PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Arm I (standard chemoradiotherapy); Arm II (experimental chemoradiotherapy)

External Beam Radiation Therapy RADIATION

Undergo radiotherapy

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Arm I (standard chemoradiotherapy)

Fludeoxyglucose F-18 DRUG

Undergo FDG PET/CT

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Arm I (standard chemoradiotherapy); Arm II (experimental chemoradiotherapy)

Image-Guided Adaptive Radiation Therapy RADIATION

Undergo individualized adaptive radiotherapy

Also known as: IGART

Arm II (experimental chemoradiotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (standard chemoradiotherapy); Arm II (experimental chemoradiotherapy)

Positron Emission Tomography PROCEDURE

Undergo FDG PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Arm I (standard chemoradiotherapy); Arm II (experimental chemoradiotherapy)

Eligibility Criteria

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

You may qualify if:

• Patients must have FDG-avid (maximum SUV \>= 4.0) (from PET scan of any date, any scanner) and histologically or cytologically proven non-small cell lung cancer
• Patients must be clinical American Joint Committee on Cancer (AJCC) stage IIIA or IIIB (AJCC, 7th ed.) with non-operable disease; non-operable disease will be determined by a multi-disciplinary treatment team, involving evaluation by at least 1 thoracic surgeon within 8 weeks prior to registration; Note: For patients who are clearly nonresectable, the case can be determined by the treating radiation oncologist and a medical oncologist, or pulmonologist
• Patients with multiple, ipsilateral pulmonary nodules (T3 or T4) are eligible if a definitive course of daily fractionated radiation therapy (RT) is planned
• History/physical examination, including documentation of weight, within 2 weeks prior to registration
• FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration
• CT scan or sim CT of chest and upper abdomen (IV contrast is recommended unless medically contraindicated) within 6 weeks prior to registration
• CT scan of the brain (contrast is recommended unless medically contraindicated) or MRI of the brain within 6 weeks prior to registration
• Pulmonary function tests, including diffusion capacity of carbon monoxide (DLCO), within 6 weeks prior to registration; patients must have forced expiratory volume in 1 second (FEV1) \>= 1.2 Liter or \>= 50% predicted without bronchodilator
• Zubrod performance status 0-1
• Able to tolerate PET/CT imaging required to be performed at an American College of Radiology (ACR) Imaging Core Laboratory (Lab) qualified facility
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (within 2 weeks prior to registration on study)
• Platelets \>= 100,000 cells/mm\^3 (within 2 weeks prior to registration on study)
• Hemoglobin (Hgb) \>= 10.0 g/dL (note: the use of transfusion or other intervention to achieve Hgb \>= 10.0 g/dL is acceptable) (within 2 weeks prior to registration on study)
• Serum creatinine within normal institutional limits or a creatinine clearance \>= 60 ml/min within 2 weeks prior to registration
• Negative serum or urine pregnancy test within 3 days prior to registration for women of childbearing potential

You may not qualify if:

• Patients with any component of small cell lung carcinoma are excluded
• Patients with evidence of a malignant pleural or pericardial effusion are excluded
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Poorly controlled diabetes (defined as fasting glucose level \> 200 mg/dL) despite attempts to improve glucose control by fasting duration and adjustment of medications; patients with diabetes will preferably be scheduled in the morning and instructions for fasting and use of medications will be provided in consultation with the patients' primary physicians
• Patients with T4 disease with radiographic evidence of massive invasion of a large pulmonary artery and tumor causing significant narrowing and destruction of that artery are excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (31)

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Sleepy Hollow

Sleepy Hollow, New York, 10591, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Cleveland Clinic Cancer Center Independence

Independence, Ohio, 44131, United States

Location

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, 44124, United States

Location

Cleveland Clinic Cancer Center Strongsville

Strongsville, Ohio, 44136, United States

Location

Cleveland Clinic Wooster Family Health and Surgery Center

Wooster, Ohio, 44691, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

McGill University Department of Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (1)

• Kong FS, Hu C, Pryma DA, Duan F, Matuszak M, Xiao Y, Ten Haken R, Siegel MJ, Hanna L, Curran WJ, Dunphy M, Gelblum D, Piert M, Jolly S, Robinson CG, Quon A, Loo BW, Srinivas S, Videtic GM, Faria SL, Ferguson C, Dunlap NE, Kundapur V, Paulus R, Siegel BA, Bradley JD, Machtay M. Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Nov 20;42(33):3935-3946. doi: 10.1200/JCO.24.00022. Epub 2024 Oct 4.

  PMID: 39365957 DERIVED

MeSH Terms

Interventions

fluoromisonidazole; Carboplatin; Radiation; Fluorodeoxyglucose F18; Paclitaxel; Taxes; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Physical Phenomena; Deoxyglucose; Deoxy Sugars; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Limitations and Caveats

The primary endpoint was designed assuming centrally reviewed progression. However, the protocol did not require submission of off-schedule CT scans which may have been used by the site for determination of progression. As a result, not all instances of progression could be centrally reviewed. For these instances, the site determination of progression was used for the primary endpoint.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

215-574-3208

Study Officials

• Feng-Ming (Spring) P Kong

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 5, 2012
• First Posted: January 10, 2012
• Study Start: February 22, 2012
• Primary Completion: August 17, 2020
• Study Completion: May 20, 2022
• Last Updated: April 21, 2026
• Results First Posted: April 21, 2026

Record last verified: 2026-04

Locations

CA (2); US (29)