Positron Emission Tomography in Predicting Response in Patients Who Are Undergoing Treatment With Pemetrexed Disodium and Cisplatin With or Without Surgery for Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

Early Positron Emission Tomography as a Predictor of Response in Neoadjuvant Chemotherapy for Non-Small Cell Lung Cancer

RATIONALE: Diagnostic procedures, such as positron emission tomography (PET), (done before, during, and after chemotherapy) may help doctors predict a patient's response to treatment and help plan the best treatment. Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well PET works in predicting response in patients who are undergoing treatment with pemetrexed disodium and cisplatin with or without surgery for stage I, stage II, or stage III non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Procedure: therapeutic conventional surgery; Procedure: adjuvant therapy; Drug: cisplatin; Drug: pemetrexed disodium; Radiation: fludeoxyglucose F 18

Detailed Description

OBJECTIVES:

Primary

• Determine the effectiveness of fludeoxyglucose F 18 positron emission tomography in predicting radiological and pathological response in patients treated with pemetrexed disodium and cisplatin with or without surgery for stage IB-IIIB non-small cell lung cancer (NSCLC).

Secondary

• Determine the safety of cisplatin and pemetrexed disodium in these patients.
• Determine the radiographic response rate, duration of response, and time to progression in patients treated with cisplatin and pemetrexed disodium.

OUTLINE: This is a multicenter study.

• Fludeoxyglucose F 18 (18FDG) positron emission tomography (PET) imaging: All patients undergo positron emission tomography (PET) imaging of the head, neck, thorax, abdomen, and pelvis. Patients receive fludeoxyglucose F 18 (^18FDG) IV followed by 45 minutes of rest. PET imaging is done over 1 hour and 8 minutes. Patients undergo PET imaging at three points during the study: 4 weeks prior to treatment, after the first cycle of treatment, and after 3 courses of chemotherapy. Some patients then undergo surgical resection of the tumor.
• Chemotherapy: Patients receive cisplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington School of Medicine
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

• Stage IB, II, IIIA, or IIIB (T4, N0-1) disease

  • Staging must have been performed 4 weeks prior to study entry with a CT scan of chest, upper abdomen, and fludeoxyglucose F 18 (^18FDG) positron emission tomography (PET) scan
  • Mediastinal evaluation and staging based on combination of CT scan and FDG-PET results
• If N1 or N2 nodes are found by FDG-PET or CT scan, metastases must be ruled out by brain MRI

• Measurable and resectable disease

  • T4 lesions must be resectable
• Eligible for curative surgery
• No malignant pleural effusion

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,250/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3.0 times ULN

Renal

• Creatinine clearance ≥ 45 mL/min

Pulmonary

• Adequate pulmonary reserve to undergo surgery

  • Predicted FEV_1 > 0.8 L after resection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• Able to take corticosteroids
• Able to take folic acid or vitamin B_12 supplements
• No other malignancy within the past 5 years except nonmelanoma skin cancer or noninvasive cervical cancer
• No concurrent serious or uncontrolled disorder that would preclude study participation

• No type I diabetes mellitus

  • Type II diabetes mellitus allowed if glucose is 80-150 mg/dL

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No concurrent prophylactic filgrastim (G-CSF)
• No concurrent thrombopoiesis-stimulating agents

Chemotherapy

• At least 5 years since prior chemotherapy

Endocrine therapy

• No concurrent anticancer hormonal therapy

Radiotherapy

• No prior radiotherapy to the chest
• No concurrent curative or palliative radiotherapy

Surgery

• Not specified

Other

• At least 30 days since prior non-FDA-approved or investigational agents
• At least 5 days since prior aspirin or other nonsteroidal anti-inflammatory agents (8 days for long-acting agents [e.g., piroxicam])
• No other concurrent anticancer therapy
• No other concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Neoadjuvant therapy, PET scan and surgery	Procedure: therapeutic conventional surgery; Procedure: adjuvant therapy; Drug: cisplatin; Drug: pemetrexed disodium; Radiation: fludeoxyglucose F 18

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positron Emission Tomography as a Predictor of Response Measured by the Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy	Number of Participants with Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy	Between days 18 and 22 prior to second chemotherapy infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Neoadjuvant Chemotherapy	The number of patients that experienced a grade 3 or higher adverse event.	Up to 4 weeks after last dose of chemotherapy
Efficacy of Neoadjuvant Chemotherapy as Measured by Radiologic Response Rate	The number of patients that had either a CR, PR or SD after the completion of chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	Up to 4 weeks after last dose of chemotherapy

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Renato Martins, MD, MPH, Seattle Cancer Care Alliance

Publications and helpful links

General Publications

• Romine PE, Martins RG, Eaton KD, Wood DE, Behnia F, Goulart BHL, Mulligan MS, Wallace SG, Kell E, Bauman JE, Patel SA, Vesselle HJ. Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome. BMC Cancer. 2019 Jan 14;19(1):70. doi: 10.1186/s12885-019-5284-2.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 26, 2005
• First Submitted That Met QC Criteria: September 26, 2005
• First Posted (Estimate): September 28, 2005

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage I non-small cell lung cancer; stage II non-small cell lung cancer
• 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; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Radiopharmaceuticals; Folic Acid Antagonists; Fluorodeoxyglucose F18; Cisplatin; Pemetrexed
• Other Study ID Numbers: 6228; P30CA015704 (U.S. NIH Grant/Contract); UWCC-6228; UWCC-UW-6228; UW-04033; LILY-UW-04033; CDR0000441239 (Registry Identifier: PDQ)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No