Stage IV Non-Small Cell Lung Cancer
Conditions
Brief summary
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.
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPemetrexed Disodium
Given IV
OTHERQuality-of-Life Assessment
QOL studies
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Baseline to 12 weeks | 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. |
| Time to Tumor Progression | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Up to 30 days | 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. |
| Overall Survival | The duration of time from the start of treatment to date of death or date of last contact, assessed up to 2 years | Examined by estimating a Kaplan-Meier survival curve using all patients enrolled. |
| Response Rate | Up to 2 years | Response rate will be estimated every 6 weeks for patients, and these estimates will be presented with confidence intervals. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Laboratory Biomarker Analysis: Correlative studies
Pemetrexed Disodium: Given IV
Quality-of-Life Assessment: QOL studies | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Patient expired before treatment | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Pemetrexed Disodium) |
|---|---|
| Age, Continuous | 70.6 Years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 13 |
| other Total, other adverse events | 12 / 13 |
| serious Total, serious adverse events | 12 / 13 |
Outcome results
Primary
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.
Time frame: Baseline to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Pemetrexed Disodium) | 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) | Baseline | 51.2821 score on a scale | Standard Error 6.6951 |
| Treatment (Pemetrexed Disodium) | 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) | 12 weeks | 58.3333 score on a scale | Standard Error 17.0693 |
p-value: 0.7044Mixed Models Analysis
Primary
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Pemetrexed Disodium) | Time to Tumor Progression | 2.0 months |
Secondary
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.
Time frame: Up to 30 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Anemia | 13 Participants |
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | CD4 lymphocyte decreased | 3 Participants |
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Febrile neutropenia | 1 Participants |
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Leukocytosis | 1 Participants |
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Lymphocyte count decreased | 9 Participants |
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Neutrophil count decreased | 11 Participants |
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Platelet count decreased | 10 Participants |
| Treatment (Pemetrexed Disodium) | Incidence of Hematologic Toxicity, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | White blood cell count decreased | 10 Participants |
Secondary
Overall Survival
Examined by estimating a Kaplan-Meier survival curve using all patients enrolled.
Time frame: The duration of time from the start of treatment to date of death or date of last contact, assessed up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Pemetrexed Disodium) | Overall Survival | 2.4 months |
Secondary
Response Rate
Response rate will be estimated every 6 weeks for patients, and these estimates will be presented with confidence intervals.
Time frame: Up to 2 years
Population: Four patients died prior to the 2nd cycle of treatment when this measure was evaulated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Pemetrexed Disodium) | Response Rate | Partial response | 1 Participants |
| Treatment (Pemetrexed Disodium) | Response Rate | Stable disease | 6 Participants |
| Treatment (Pemetrexed Disodium) | Response Rate | Progressive disease | 2 Participants |