Study of Positron Emission Tomography and Computed Tomography in Guiding Radiation Therapy in Patients With Stage III Non-small Cell Lung Cancer

NCT ID: NCT01507428

Last Updated: 2021-04-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-22

Study Completion Date

2021-08-01

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine whether tumor dose can be escalated to improve the freedom from local-regional progression-free (LRPF) rate at 2 years when an individualized adaptive radiation treatment (RT) plan is applied by the use of a fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scan acquired during the course of fractionated RT in patients with inoperable stage III non-small cell lung cancer (NSCLC). (National Surgical Adjuvant Breast and Bowel Project \[NSABP\], Radiation Therapy Oncology Group \[RTOG\], Gynecologic Oncology Group \[GOG\] \[NRG\] Oncology) II. To determine whether the relative change in standard uptake value (SUV) peak from the baseline to the during-treatment FDG-PET/CT, defined as (during-treatment SUVpeak - baseline SUVpeak)/baseline SUV peak x 100%, can predict the LRPF rate with a 2-year follow up. (Eastern Cooperative Oncology Group \[ECOG\]-American College of Radiology Imaging Network \[ACRIN\])

SECONDARY OBJECTIVES:

I. To determine whether an individualized dose escalation improves overall survival (OS), progression-free survival (PFS), lung cancer cause-specific survival, and delays time to local-regional progression compared to a conventional RT plan. (NRG Oncology) II. To compare the rate of severe (grade 3+ Common Terminology Criteria for Adverse Events \[CTCAE\], v. 4) radiation-induced lung toxicity (RILT) defined as severe RILT pneumonitis or clinical fibrosis. (NRG Oncology) III. To compare other severe adverse events, including grade 3+ (CTCAE, v. 4) esophagitis or grade 2 pericardial effusions, or any grade cardiac adverse events related to chemoradiation between a PET/CT-guided adaptive approach and a conventional RT plan. (NRG Oncology) IV. To evaluate the association of baseline 18F-fluoromisonidazole (FMISO), a PET/CT imaging agent uptake (tumor-to-blood pool ratio) with LRPF (i.e., the assessment of using baseline FMISO-PET uptake as a prognostic marker). (ECOG-ACRIN) V. To determine if the relative change in SUVpeak from baseline to during-treatment FDG-PET/CT and/or baseline FMISO uptake (tumor-to-blood pool ratio) predicts the differential benefit of the adaptive therapy, i.e., the association of uptake parameters with LRPF rate depending on the assigned treatment thus, assessing if these uptake parameters can be useful in guiding therapies, i.e., predictive markers. (ECOG-ACRIN) VI. To determine if other PET-imaging uptake parameters (SUV peak during-treatment for FDG-PET, maximum SUV, or relative change of maximum SUVs from pre- to during-treatment FDG-PET/CT, change in metabolic tumor volume, FMISO total hypoxic volume, FMISO tumor to mediastinum ratio, EORTC or University of Michigan/Kong's response criteria) will predict OS, LRPF rate, and lung cancer cause-specific (LCS) survival as well as to explore the optimal threshold for differentiating responders from non-responders. (ECOG-ACRIN)

CORRELATIVE SCIENCE OBJECTIVES:

I. To study whether a model of combining current clinical and/or imaging factors with blood markers, including osteopontin (OPN) \[for hypoxia marker\], carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1 (for tumor burden), and interleukin (IL)-6 (inflammation) will predict the 2-year LRPF rate and survival better than a current model using clinical factors and radiation dose as well as imaging factors.

II. To determine/validate whether a model of combining mean lung dose (MLD), transforming growth factor beta1 (TGF beta1) and IL-8 will improve the predictive accuracy for clinical significant RILT better comparing to the current model of using MLD alone.

III. To explore, in a preliminary manner, whether proteomic and genomic markers in the blood prior to and during the early course of treatment are associated with tumor response after completion of treatment, LRPF rate, PFS, OS, and pattern of failure and treatment-related adverse events, such as radiation pneumonitis, esophagitis, and pericardial effusion. (exploratory)

OUTLINE:

Prior to treatment, patients undergo fludeoxyglucose F 18 (FDG) positron emission tomography (PET) and computed tomography (CT) scans at baseline and periodically during study. A subset of patients also undergo 18F-fluoromisonidazole PET/CT scan at baseline. Patients are randomized to 1 of 2 treatment arms:

ARM I (standard chemoradiotherapy): Patients undergo radiotherapy once daily (QD) 5 days a week for 30 fractions. Patients also receive paclitaxel intravenously (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.

ARM II (experimental chemoradiotherapy): 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.

CONSOLIDATION CHEMOTHERAPY: Beginning 4-6 weeks after chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (standard chemoradiotherapy)

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.

Group Type ACTIVE_COMPARATOR

18F-Fluoromisonidazole

Intervention Type DRUG

Undergo FMISO PET/CT (Correlative studies)

Carboplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo FDG PET/CT

Computed Tomography

Intervention Type PROCEDURE

Undergo FMISO PET/CT (Correlative studies)

External Beam Radiation Therapy

Intervention Type RADIATION

Undergo radiotherapy

Fludeoxyglucose F-18

Intervention Type DRUG

Undergo FDG PET/CT

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo FDG PET/CT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo FMISO PET/CT (Correlative studies)

Arm II (experimental chemoradiotherapy)

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.

Group Type EXPERIMENTAL

18F-Fluoromisonidazole

Intervention Type DRUG

Undergo FMISO PET/CT (Correlative studies)

Carboplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo FDG PET/CT

Computed Tomography

Intervention Type PROCEDURE

Undergo FMISO PET/CT (Correlative studies)

Fludeoxyglucose F-18

Intervention Type DRUG

Undergo FDG PET/CT

Image-Guided Adaptive Radiation Therapy

Intervention Type RADIATION

Undergo individualized adaptive radiotherapy

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Paclitaxel

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo FDG PET/CT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo FMISO PET/CT (Correlative studies)

Interventions

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18F-Fluoromisonidazole

Undergo FMISO PET/CT (Correlative studies)

Intervention Type DRUG

Carboplatin

Given IV

Intervention Type DRUG

Computed Tomography

Undergo FDG PET/CT

Intervention Type PROCEDURE

Computed Tomography

Undergo FMISO PET/CT (Correlative studies)

Intervention Type PROCEDURE

External Beam Radiation Therapy

Undergo radiotherapy

Intervention Type RADIATION

Fludeoxyglucose F-18

Undergo FDG PET/CT

Intervention Type DRUG

Image-Guided Adaptive Radiation Therapy

Undergo individualized adaptive radiotherapy

Intervention Type RADIATION

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Paclitaxel

Given IV

Intervention Type DRUG

Positron Emission Tomography

Undergo FDG PET/CT

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo FMISO PET/CT (Correlative studies)

Intervention Type PROCEDURE

Other Intervention Names

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18F-MISO 18F-Misonidazole FMISO Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo CAT CAT Scan Computerized Axial Tomography Computerized Tomography CT CT Scan tomography CAT CAT Scan Computerized Axial Tomography Computerized Tomography CT CT Scan tomography Definitive Radiation Therapy EBRT External Beam Radiation External Beam Radiotherapy External Beam RT external radiation External Radiation Therapy external-beam radiation Radiation, External Beam 18FDG FDG Fludeoxyglucose (18F) fludeoxyglucose F 18 Fludeoxyglucose F18 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose Fluorodeoxyglucose F18 IGART Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging

Eligibility Criteria

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Inclusion Criteria

* 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
* Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study
* The patient must provide study-specific informed consent prior to study entry

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NRG Oncology

OTHER

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Feng-Ming (Spring) P Kong

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

Augusta University Medical Center

Augusta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Sleepy Hollow

Sleepy Hollow, New York, United States

Site Status

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Cancer Center Independence

Independence, Ohio, United States

Site Status

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

Site Status

Cleveland Clinic Cancer Center Strongsville

Strongsville, Ohio, United States

Site Status

Cleveland Clinic Wooster Family Health and Surgery Center

Wooster, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Reading Hospital

West Reading, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

McGill University Department of Oncology

Montreal, Quebec, Canada

Site Status

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 39365957 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2012-00107

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000721619

Identifier Type: -

Identifier Source: secondary_id

RTOG-1106/ACRIN-6697

Identifier Type: -

Identifier Source: secondary_id

RTOG-1106

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-1106

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA021661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-00107

Identifier Type: -

Identifier Source: org_study_id

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