Pemetrexed Disodium in Treating Patients With Stage IV Non-small Cell Lung Cancer and ECOG Performance Status 3

A Pilot Study Evaluating Pemetrexed in ECOG Performance Status 3 Patients With Stage IV Non-squamous Non-small Cell Lung Cancer

This pilot phase II trial studies how well pemetrexed disodium works in treating patients with stage IV non-small cell lung cancer and an Eastern Cooperative Oncology Group (ECOG) performance status of 3. Performance status means how well patients are able to perform daily activities and care for themselves. Patients with a performance status of 3 have a limited ability to move around. Currently, only patients who are able to perform most of their daily activities may receive chemotherapy, due to the side effects it may cause. Pemetrexed disodium causes fewer side effects than many chemotherapy drugs and may help treat patients with stage IV non-small cell lung cancer and a lower performance status.

Study Overview

• Status: Completed
• Conditions: Stage IV Non-Small Cell Lung Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Pemetrexed Disodium; Other: Quality-of-Life Assessment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the effect of single agent pemetrexed (pemetrexed disodium) on tumor progression in ECOG performance status 3 patients with stage IV non-squamous histology non-small cell lung cancer in a single arm pilot study.

II. To evaluate the effect of single agent pemetrexed on quality of life in ECOG performance status 3 patients with stage IV non-squamous histology non-small cell lung cancer in a single arm pilot study.

SECONDARY OBJECTIVES:

I. To evaluate toxicity associated with single agent pemetrexed on tumor progression in ECOG performance status 3 patients with stage IV non-squamous histology non-small cell lung cancer in a single arm pilot study.

OUTLINE:

Patients receive pemetrexed disodium intravenously (IV) over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 30 days and then every 6 weeks thereafter.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center of Wake Forest University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must have histologically confirmed Stage IV non-squamous histology non-small cell lung cancer
• ECOG performance status of 3
• Sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK) and ROS proto-oncogene 1, receptor tyrosine kinase (ROS-1) mutations are either negative or unknown
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Creatinine clearance >= 45 mL/min
• 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
• Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document
• Ability to understand and complete the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) instruments

Exclusion Criteria:

• Patients who have previously received chemotherapy for non-small cell lung cancer, or have received radiotherapy within 2 weeks prior to entering the study, or who have not recovered from adverse events due to treatment more than 2 weeks earlier
• Patients whose tumors are positive for the sensitizing EGFR mutation
• Patients whose tumors are positive for the sensitizing ALK fusion
• Patients whose tumors are positive for the sensitizing ROS-1 fusion
• Patients may not be receiving any other investigational agents
• Patients with symptomatic or recurrent brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed
• Pregnant women are excluded from this study; breastfeeding should be discontinued

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: Treatment (pemetrexed disodium); Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Quality-of-Life Assessment and Laboratory Biomarker Analysis.	Other: Laboratory Biomarker Analysis; Correlative studies; 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; Other: Quality-of-Life Assessment; QOL studies; Other Names: Quality of Life Assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life (QOL), Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and QLQ-Lung Cancer 13-item (LC13)	Quality of life will be assessed at each treatment time (i.e. every three weeks). A longitudinal mixed models analysis will be used to look at QOL over the time course. A paired t-test will also be calculated to see if the average change is more than 0 (worsening) versus a two-sided alternative that the difference is 0 or better. Score range from 0-100 (1 = not at all, 2 = a little, 3 = quite a bit, or 4 = very much). The higher the score, the greater the change in the quality of life for the worse.	Baseline to 12 weeks
Time to Tumor Progression	It will be determined whether each patient has a progression (or dies) before or after 12 weeks. A 95% exact (Clopper Pearson) confidence interval will then be around the proportion with PFS greater than or equal to 12 weeks. If this confidence interval includes 50% then that would provide evidence that the therapy is potentially promising. If the upper bound of the confidence interval does not include 50% then this would indicate that the treatment may not be promising for patients. In addition, a Kaplan Meier survival curve will be constructed to describe the time to progression data.	The duration of time from the start of treatment to the time of progression, death, or date of last contact, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	The number and type of toxicities observed during this protocol will be estimated, focusing on unexpected grade 3 or higher toxicities. No formal statistical tests will be done on these estimates.	Up to 30 days
Overall Survival	Examined by estimating a Kaplan-Meier survival curve using all patients enrolled.	The duration of time from the start of treatment to date of death or date of last contact, assessed up to 2 years
Response Rate	Response rate will be estimated every 6 weeks for patients, and these estimates will be presented with confidence intervals.	Up to 2 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stefan Grant, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): April 19, 2018
• Study Completion (Actual): October 7, 2022

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: April 22, 2015
• First Posted (Estimated): April 27, 2015

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: August 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; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: IRB00032417; P30CA012197 (U.S. NIH Grant/Contract); NCI-2015-00596 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 62115; CCCWFU # 62115 (Other Identifier: Comprehensive Cancer Center of Wake Forest University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No