Fludeoxyglucose F-18 PET/CT in Predicting Response to Chemotherapy in Patients With Stage IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

Role of Early 18F-FDG-PET/CT Scan in Predicting Mediastinal Downstaging With Neoadjuvant Chemotherapy in Resectable Stage III A NSCLC

This phase II trial studies how well fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) works in predicting response to chemotherapy in patients with stage IIIA non-small cell lung cancer that can be removed by surgery (resectable). Performing diagnostic procedures, such as fludeoxyglucose F-18 PET/CT, after one course of chemotherapy may help doctors predict a patient's response to treatment earlier and help plan the best treatment.

Study Overview

• Status: Withdrawn
• Conditions: Stage IIIA Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Docetaxel; Drug: Pemetrexed Disodium; Drug: Gemcitabine Hydrochloride; Procedure: Computed Tomography; Radiation: Fludeoxyglucose F-18; Procedure: Positron Emission Tomography

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate whether percent change in maximum standardized uptake value (SUVmax) on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes can predict mediastinal downstaging in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the predictive accuracy for mediastinal downstaging of two other FDG-PET/CT-based markers measured on mediastinal lymph nodes: SUVmax at T1 and change of SUVmax from T0 to T1.

II. To evaluate the predictive accuracy for mediastinal downstaging of the FDG-PET/CT-based markers measured on the primary tumor, include percent change of peak standardized uptake value (SUVpeak) (based on PET Response Criteria in Solid Tumors [PERCIST] criteria), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) from T0 to T1.

III. To evaluate whether percent change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes can predict overall survival (OS).

OUTLINE:

Patients undergo fludeoxyglucose F-18 PET/CT at baseline and after course 1 of chemotherapy. Patients undergo 1 of 3 chemotherapy regimens at the discretion of the investigator.

CHEMOTHERAPY REGIMEN 1: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, and 8. Patients also receive cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CHEMOTHERAPY REGIMEN 2: Patients receive docetaxel IV over 60 minutes and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CHEMOTHERAPY REGIMEN 3: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 60 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 every 6 months for 5 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • ECOG-ACRIN Cancer Research Group

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient must have stage IIIA non-small cell lung cancer (T1-3N2) per American Joint Committee on Cancer (AJCC) 7th edition and must be considered to be surgically resectable
• Patients must be assessed by surgeons and are considered surgically resectable
• Mediastinal nodal metastases (N2) disease must be confirmed histologically
• Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
• Required imaging studies obtained within four weeks prior to registration
• White blood cell (WBC) >= 4000 mm^3 or granulocyte count at least 2,000/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 10.0g/dL
• Total bilirubin < 1.5 mg/dL
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 3 x upper limit of normal (ULN)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN
• Alkaline phosphatase < 3 x ULN
• Calculated/estimated or measured creatinine clearance at least 50 ml/min; note: creatinine clearance should be calculated using the Cockcroft-Gault formula; patients who will receive pemetrexed/cisplatin therapy must be obtained within 2 weeks of registration
• Patients cannot have hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years of registration; (prior surgery, biologic therapy, hormonal therapy, or radiation therapy for a malignancy over 5 years prior to enrollment that is not considered cured is acceptable)
• Patients must not have any history of other cancer within 5 years from registration with the exception of in situ carcinoma of the cervix, in situ carcinoma of the breast or completely resected non-melanoma skin cancer
• Patients may not have received prior chemotherapy or radiation therapy for lung cancer
• Patients with a history of myocardial infarction are eligible if the event occurred > 6 months prior to entry
• Patients must not have any clinically significant ongoing, active or serious infection, symptomatic or uncontrolled congestive heart failure, active angina, symptomatic or uncontrolled cardiac arrhythmia or any other medical condition or psychiatric illness/social situations that would limit compliance with study requirements
• Patents must have no contraindication to cisplatin chemotherapy including no clinically significant hearing loss unless willing to accept the potential of further loss of hearing, no symptomatic peripheral neuropathy
• Women must not be pregnant or breast-feeding
• All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
• A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study
• Patients must not have received any study therapies prior to registration

• Pemetrexed/cisplatin therapy; note: patients who will receive pemetrexed/cisplatin therapy must meet all eligibility criteria below:

  • Patients assigned to pemetrexed/cisplatin therapy must NOT have squamous cell histology
  • Calculated creatinine clearance must be obtained within 2 weeks of registration and calculated creatinine clearance (CrCl) must be >= 45mL/min using the standard Cockcroft and Gault formula, or the measured glomerular filtration rate (GFR) using the appropriate radiolabeled method (51-CrEDTA or Tc99m-DTPA) must be used to calculate CrCl
• Patients should have no contraindications for FDG-PET/CT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (18F-FDG PET/CT); Patients undergo fludeoxyglucose F-18 PET/CT at baseline and after course 1 of chemotherapy. Patients undergo 1 of 3 chemotherapy regimens at the discretion of the investigator. CHEMOTHERAPY REGIMEN 1: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, and 8. Patients also receive cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY REGIMEN 2: Patients receive docetaxel IV over 60 minutes and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. CHEMOTHERAPY REGIMEN 3: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Docetaxel; Given IV; Other Names: Taxotere; Docecad; RP56976; Taxotere Injection Concentrate; Drug: Pemetrexed Disodium; Given IV; Other Names: Alimta; LY231514; N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: Gemzar; dFdCyd; Difluorodeoxycytidine Hydrochloride; LY-188011; Procedure: Computed Tomography; Undergo 18F-FDG PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; tomography; CT SCAN; Radiation: Fludeoxyglucose F-18; Undergo 18F-FDG PET/CT; Other Names: 18FDG; FDG; fludeoxyglucose F 18; Fludeoxyglucose F18; Fluorine-18 2-Fluoro-2-deoxy-D-Glucose; Fluorodeoxyglucose F18; Procedure: Positron Emission Tomography; Undergo 18F-FDG PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PET SCAN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of mediastinal downstaging	The predictive accuracy of the percent change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes will be estimated by the area under a receiver operating characteristic (ROC) curve (AUC) with a 95% confidence interval (CI). The AUC will be estimated empirically. The reference standard for the ROC analysis will be the presence or absence of mediastinal downstaging, as assessed by thoracotomy, mediastinoscopy, mediastinotomy, endoscopic bronchoscopic ultrasound (EBUS), or endoscopic ultrasound (EUS).	Up to 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of SUVmax	The predictive accuracy of the change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal lymph nodes will be estimated by the ROC AUC with a 95% CI. The AUC will be estimated empirically.	Baseline to 3 weeks
Overall survival	Time-dependent ROC analysis will be used to determine the predictive accuracy of percent change in SUVmax on FDG-PET/CT from T0 to T1 measured on mediastinal to predict overall survival.	Up to 5 years
Percent change of metabolic tumor volume	The predictive accuracy of percent change of metabolic tumor volume from T0 to T1 from primary tumor will be measured by the ROC AUC with a 95% CI. The AUC will be estimated empirically.	Baseline to 3 weeks
Percent change of SUVpeak	The predictive accuracy of percent change of SUVpeak from T0 to T1 from primary tumor will be measured by the ROC AUC with a 95% CI. The AUC will be estimated empirically.	Baseline to 3 weeks
Percent change of TLG	The predictive accuracy of percent change of TLG from T0 to T1 from primary tumor will be measured by the ROC AUC with a 95% CI. The AUC will be estimated empirically.	Baseline to 3 weeks
SUVmax	The predictive accuracy of SUVmax at T1 will be estimated by the ROC AUC with a 95% CI. The AUC will be estimated empirically.	At 3 weeks

Collaborators and Investigators

• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Leora Horn, ECOG-ACRIN Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Estimated): November 19, 2015
• Primary Completion (Actual): January 31, 2017
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (Estimated): November 18, 2015

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Radiopharmaceuticals; Folic Acid Antagonists; Docetaxel; Fluorodeoxyglucose F18; Cisplatin; Pemetrexed; Deoxyglucose; Gemcitabine
• Other Study ID Numbers: EA5123 (Other Identifier: CTEP); U10CA180820 (U.S. NIH Grant/Contract); NCI-2015-01054 (Registry Identifier: CTRP (Clinical Trial Reporting Program))