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A Comparison of FLT to FDG PET/CT in the Early Assessment of Chemotherapy Response in Stage IB-IIIA Resectable NSCLC

Primary Purpose

Recurrent Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Non-Small Cell Lung Carcinoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Cisplatin

Docetaxel

FDG

FLT

PET/CT

Surgery

About this trial

This is an interventional treatment trial for Recurrent Non-Small Cell Lung Carcinoma

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have histologically or cytologically confirmed clinical stage IB - IIIA non-small cell lung cancer; stage IV patients with oligometastatic disease with metastases that have been treated definitively with radiation or surgery are also eligible (ie: solitary brain or adrenal metastasis); mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible; note: tissue samples from biopsy confirmation will be required
Patients must be surgically resectable as determined by a thoracic surgeon
Patients must have measurable disease per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with spiral CT scan
Life expectancy of greater than 12 weeks
ECOG performance status < 1
Leukocytes >= 3,000/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,000/uL
Total bilirubin =< 1.5 x institutional upper limit of normal
AST (SGOT) =< 1.5 x institutional upper limit of normal
Alkaline phosphatase =< 2.5 x institutional upper limit of normal
Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/1.73 m2 for patients with creatinine levels above institutional normal
Fasting screening blood glucose =< 200 mg/dL
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with either agent

Exclusion Criteria:

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Patients may not be receiving any other investigational agents
Patients must not have received prior systemic chemotherapy or radiation therapy for lung cancer; prior systemic chemotherapy or radiation for other malignancies over three years prior to study enrollment may be allowed at the discretion of the principal medical investigator
Prior malignancy in the past 3 years, other than non-melanoma skin cancer and in situ carcinoma of the cervix
Patients who report a hearing deficit at baseline, even if it does not require a hearing aid or intervention, or interfere with activities of daily life (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher)
Peripheral neuropathy > CTCAE grade 1
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, docetaxel, or other agents used in the study
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric/social situations that would limit compliance with study requirements
HIV-positive patients on combination antiretroviral therapy are ineligible
Inability to comply with study and/or follow-up procedures

Sites / Locations

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Ohio State University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Patients receive docetaxel IV and cisplatin IV on day 1. Treatment repeats every 3 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo FDG PET/CT, FLT PET/CT, and thoracic CT at baseline and the end of cycles 1 and 2 and then undergo surgery.

Outcomes

Primary Outcome Measures

Change in 18F-Fluorothymidine (FLT) Uptake

Will be calculated by subtracting the uptake of the scan after the first cycle of chemotherapy from the uptake of the pre-treatment scan.. Change in FLT uptake will be measured using the maximum standard uptake value adjusted for lean body mass (SULmax), which is a measure of how much radiotracer (in this case FLT) is being consumed by cells.

Change in FLT Uptake

Will be calculated by subtracting the uptake of the scan after the second cycle of chemotherapy from the uptake of the pre-treatment scan.

Change in FLT Uptake in Responders and Non-responders

Unadjusted analysis will be performed utilizing students t-tests. If the data appears non-normal, the Wilcox on rank-sum test will be used rather than the t-test. Adjusted analysis will be performed utilizing logistic regression.

Secondary Outcome Measures

Change in 18F-Fluorodeoxyglucose (FDG) Uptake

Will be calculated by subtracting the baseline FDG uptake from the post-cycle 2 uptake (as measured by SULmax).

Overall Response Rate Reported as a Proportion of the Total Number of Patients Who Received at Least One Cycle of Therapy Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)

RECIST version 1.1 was utilized for this outcome measure. A detailed description of RECIST 1.1 can be found here: Nishino M, Jackman DM, Hatabu H, Yeap BY, Cioffredi LA, Yap JT, et al. New Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol 2010;195:W221-8.

Full Information

NCT ID

NCT00963807

First Posted

August 18, 2009

Last Updated

January 27, 2017

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00963807

Brief Title

A Comparison of FLT to FDG PET/CT in the Early Assessment of Chemotherapy Response in Stage IB-IIIA Resectable NSCLC

Official Title

Phase II Single-Arm Trial Comparing the Use of FLT PET to Standard Computed Tomography to Assess the Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable Non-small Cell Lung Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

August 2012 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is being done to compare a special type of Positron Emission Tomography (PET) scan with CT scan in patients with surgically removable lung cancer to see which method is more useful in measuring a response to treatment. A PET scan uses small amounts of radioactive material injected into the blood to show the internal workings of the body. In this study, we will use two radioactive materials: 18F-FLT (referred to as FLT) and 18F-FDG (referred to as FDG). FDG is used routinely in the staging of lung cancer and is approved by the FDA for that purpose. FLT is used in the special type of PET scan being assessed by this study. In addition the study will assess the effects of the combination of docetaxel and cisplatin (chemotherapeutic drugs) on certain pathological characteristics of the tumor. The combination of docetaxel and cisplatin is approved by the Food and Drug Administration (FDA) for the treatment of advanced/metastatic NSCLC (non-small cell lung cancer). It is not approved for use in patients who have surgically removable NSCLC. In such cases cisplatin is used as a single drug therapy before surgery. The FDA is allowing the use of docetaxel along with cisplatin in this research study.

Detailed Description

PRIMARY OBJECTIVES: I. To determine if the absolute decrease measured in primary tumor 18 F-F-3'-fluoro-3'-deoxy-L-thymidine (FLT) uptake (standard uptake value [SUV] and influx constant [Ki]) between pre-treatment imaging and imaging after the first cycle of therapy differs in patients categorized as responders or non-responders based on Response Evaluation Criteria in Solid Tumors (RECIST) measured with computed tomography (CT) after the second cycle of therapy. SECONDARY OBJECTIVES: I. To determine if the absolute decrease measured in primary tumor FDG uptake (SUV) between pre-treatment imaging and imaging after the first cycle of therapy differs in patients categorized as responders or non-responders based on RECIST measured with CT after the second cycle of therapy. II. To assess the effects of the combination of docetaxel and cisplatin on fractional tumor viability and proliferative fraction pre and post treatment and to correlate these with the PET SUV data for both tracers. III. To assess the methylation status of the checkpoint with forkhead and ring finger domains gene (CHFR) gene from pre-treatment tumor biopsies and correlate methylation status post treatment with clinical and pathologic response. OUTLINE: Patients receive docetaxel intravenously (IV) and cisplatin IV on day 1 and dexamethasone orally (PO) twice daily (BID). Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo FDG PET/CT, FLT PET/CT, and thoracic CT at baseline and the end of courses 1 and 2 and then undergo surgery. After completion of study treatment, patients are followed up for 4-6 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Non-Small Cell Lung Carcinoma, Stage IIB Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

Other Intervention Name(s)

CAT, CAT Scan, Computed Tomography, Computerized Axial Tomography, Computerized Tomography, CT SCAN, tomography

Intervention Description

Undergo FDG PET/CT, FLT PET/CT and thoracic CT

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

RP56976, Taxotere, Taxotere Injection Concentrate

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

FDG

Other Intervention Name(s)

18FDG, fludeoxyglucose F 18, FLUDEOXYGLUCOSE F-18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Intervention Description

Undergo FDG PET/CT

Intervention Type

Drug

Intervention Name(s)

FLT

Other Intervention Name(s)

18F-FLT, 3'-deoxy-3'-(18F) fluorothymidine, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F 18, FLUOROTHYMIDINE F-18

Intervention Description

Undergo FLT PET/CT

Intervention Type

Procedure

Intervention Name(s)

PET/CT

Other Intervention Name(s)

Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Intervention Description

Undergo FDG PET/CT and FLT PET/CT

Intervention Type

Procedure

Intervention Name(s)

Surgery

Other Intervention Name(s)

Therapeutic Conventional Surgery

Intervention Description

Undergo surgery

Primary Outcome Measure Information:

Title

Change in 18F-Fluorothymidine (FLT) Uptake

Description

Time Frame

Baseline and 3 weeks

Title

Change in FLT Uptake

Description

Will be calculated by subtracting the uptake of the scan after the second cycle of chemotherapy from the uptake of the pre-treatment scan.

Time Frame

Baseline and 6 weeks

Title

Change in FLT Uptake in Responders and Non-responders

Description

Time Frame

Baseline and 6 weeks

Secondary Outcome Measure Information:

Title

Change in 18F-Fluorodeoxyglucose (FDG) Uptake

Description

Will be calculated by subtracting the baseline FDG uptake from the post-cycle 2 uptake (as measured by SULmax).

Time Frame

Baseline and 6 weeks

Title

Overall Response Rate Reported as a Proportion of the Total Number of Patients Who Received at Least One Cycle of Therapy Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)

Description

Time Frame

Up to 6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have histologically or cytologically confirmed clinical stage IB - IIIA non-small cell lung cancer; stage IV patients with oligometastatic disease with metastases that have been treated definitively with radiation or surgery are also eligible (ie: solitary brain or adrenal metastasis); mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible; note: tissue samples from biopsy confirmation will be required Patients must be surgically resectable as determined by a thoracic surgeon Patients must have measurable disease per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with spiral CT scan Life expectancy of greater than 12 weeks ECOG performance status < 1 Leukocytes >= 3,000/uL Absolute neutrophil count >= 1,500/uL Platelets >= 100,000/uL Total bilirubin =< 1.5 x institutional upper limit of normal AST (SGOT) =< 1.5 x institutional upper limit of normal Alkaline phosphatase =< 2.5 x institutional upper limit of normal Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/1.73 m2 for patients with creatinine levels above institutional normal Fasting screening blood glucose =< 200 mg/dL Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with either agent Exclusion Criteria: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Patients may not be receiving any other investigational agents Patients must not have received prior systemic chemotherapy or radiation therapy for lung cancer; prior systemic chemotherapy or radiation for other malignancies over three years prior to study enrollment may be allowed at the discretion of the principal medical investigator Prior malignancy in the past 3 years, other than non-melanoma skin cancer and in situ carcinoma of the cervix Patients who report a hearing deficit at baseline, even if it does not require a hearing aid or intervention, or interfere with activities of daily life (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher) Peripheral neuropathy > CTCAE grade 1 History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, docetaxel, or other agents used in the study Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric/social situations that would limit compliance with study requirements HIV-positive patients on combination antiretroviral therapy are ineligible Inability to comply with study and/or follow-up procedures

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Richard Wahl

Organizational Affiliation

Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Ohio State University Comprehensive Cancer Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

A Comparison of FLT to FDG PET/CT in the Early Assessment of Chemotherapy Response in Stage IB-IIIA Resectable NSCLC

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