Pleural Neoplasms
Conditions
Brief summary
This study aims to determine how successful the chemotherapy regimen of Pemetrexed plus cisplatin before surgery is at killing all the tumor so that none is left at the time of surgery. Following surgery, all eligible patients will receive radiation to the chest. How patients respond, whether the cancer returns and if so, where, will also be monitored.
Interventions
DRUGpemetrexed
500 mg/m2, intravenous (IV), every 21 days x 4 cycles
DRUGcisplatin
75 mg/m2, intravenous (IV), every 21 days x 4 cycles
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
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 will be clinically staged using AJCC/UICC TNM staging criteria. Eligible stages: 1. Patients must be M0 2. Patients with T1, T2, and T3 disease (without cardiac involvement) are eligible (T status can be established clinically and radiologically or at exploratory thoracotomy without surgical resection 3. Patients with N0, N1,or N2 disease are eligible * Performance status of 0 to 1 on the ECOG performance status schedule. * No prior systemic chemotherapy and no prior intracavitary cytotoxic drugs or immunomodulators, unless given for the purpose of chemical pleurodesis * No previous radiation therapy * Estimated life expectancy of at least 12 weeks
Exclusion criteria
Patients will be excluded if they meet ANY of the following criteria: * Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry * Have previously completed or withdrawn from this study or any other study investigating pemetrexed * Pregnancy or breast-feeding * Serious concomitant systemic disorders (i.e. active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study * Second active primary malignancy (except in situ carcinoma of the cervix, adequately treated non-melanomatous carcinoma of the skin, low grade (Gleason score less than or equal to 6), localized adenocarcinoma of the prostate or other malignancy treated at least 2 years previously with no evidence of recurrence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response | Surgery (at least 3 weeks post last dose of chemotherapy, up to a maximum interval of 8 weeks) | Number of participants with results of pathological review that indicated a complete response. Pathological complete response should be evaluated at the time of surgery (Extrapleural Pneumonectomy \[EPP\]). Resected tissue or pleural fluid should be sent for pathological and histological evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The 1 and 2 Year Disease-Free Survival Rate (Percentage) | 1 year and 2 years | Kaplan-Meier estimates of the percentage of participants still alive at 1-year and 2-years, based upon the total number of participants who had surgery. |
| Overall Tumor Response | baseline to measured progressive disease | The frequency of best overall tumor response summarized by response category. The best (unconfirmed) response recorded from the start of chemotherapy treatment until disease progression/recurrence, start of any further anti-tumor therapy, or time of surgery whichever comes first. |
| Time to Treatment Failure | baseline to stopping treatment | Time to relapse (treatment failure) is measured in months and calculated as (Date of first surgery - Date of first relapse after surgery + 1)/(365.25/12). Time to relapse will be censored at the date of the last visit or start date of further anti-tumor therapy or intervention, whichever comes first. |
| Time to Progressive Disease | baseline to measured progressive disease | Number of months between the first dose date and the date of first disease progression or death as a result of any cause, whichever comes first. |
| Overall Survival Time | baseline to date of death from any cause | Number of months between the first dose date and the date of death as a result of any cause. Overall survival time calculated as (Date of death - First dose date + 1)/(365.25/12). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy) | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Clinical Relapse | 1 |
| Overall Study | Death from Other Causes | 3 |
| Overall Study | Death from Study Disease | 2 |
| Overall Study | Death from Study Drug Toxicity | 2 |
| Overall Study | Lack of Efficacy, Physician Perception | 3 |
| Overall Study | Lack of Efficacy, Progressive Disease | 14 |
| Overall Study | Protocol Entry Criteria Not Met | 2 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Pemetrexed |
|---|---|
| Age Continuous | 61.1 years STANDARD_DEVIATION 9.38 |
| Disease Stage at Time of Study Entry Stage IA | 3 participants |
| Disease Stage at Time of Study Entry Stage IB | 3 participants |
| Disease Stage at Time of Study Entry Stage II | 33 participants |
| Disease Stage at Time of Study Entry Stage III | 35 participants |
| Disease Stage at Time of Study Entry Stage IV | 1 participants |
| Disease Stage at Time of Study Entry Unknown/Not Available | 2 participants |
| Eastern Cooperative Oncology Group Performance Status 0 - Fully active and asymptomatic | 28 participants |
| Eastern Cooperative Oncology Group Performance Status 1 - Ambulatory with symptoms | 47 participants |
| Eastern Cooperative Oncology Group Performance Status 2 - In bed < 50% of time | 2 participants |
| Initial Pathological Diagnosis Epithelial Mesothelioma | 62 participants |
| Initial Pathological Diagnosis Mixed Cell Mesothelioma | 2 participants |
| Initial Pathological Diagnosis Other | 12 participants |
| Initial Pathological Diagnosis Sarcomatoid Mesothelioma | 1 participants |
| Race/Ethnicity African | 1 participants |
| Race/Ethnicity Caucasian | 71 participants |
| Race/Ethnicity East/Southeast Asian | 1 participants |
| Race/Ethnicity Hispanic | 2 participants |
| Race/Ethnicity Western Asian | 2 participants |
| Region of Enrollment United States | 77 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 56 Participants |
| Time from Initial Pathological Diagnosis to Enrollment | 2.19 months STANDARD_DEVIATION 2.909 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 77 / — |
| serious Total, serious adverse events | 15 / — |
Outcome results
Primary
Pathological Complete Response
Number of participants with results of pathological review that indicated a complete response. Pathological complete response should be evaluated at the time of surgery (Extrapleural Pneumonectomy \[EPP\]). Resected tissue or pleural fluid should be sent for pathological and histological evaluation.
Time frame: Surgery (at least 3 weeks post last dose of chemotherapy, up to a maximum interval of 8 weeks)
Population: All participants who had undergone surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed | Pathological Complete Response | 3 participants |
Secondary
Overall Survival Time
Number of months between the first dose date and the date of death as a result of any cause. Overall survival time calculated as (Date of death - First dose date + 1)/(365.25/12).
Time frame: baseline to date of death from any cause
Population: All participants who had undergone surgery.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pemetrexed | Overall Survival Time | 21.85 months |
Secondary
Overall Tumor Response
The frequency of best overall tumor response summarized by response category. The best (unconfirmed) response recorded from the start of chemotherapy treatment until disease progression/recurrence, start of any further anti-tumor therapy, or time of surgery whichever comes first.
Time frame: baseline to measured progressive disease
Population: Intention to Treat analysis. All enrolled participants who were eligible for the treatment, whether or not they received the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed | Overall Tumor Response | Complete Response | 1 participants |
| Pemetrexed | Overall Tumor Response | Partial Response | 24 participants |
| Pemetrexed | Overall Tumor Response | Stable Disease | 36 participants |
| Pemetrexed | Overall Tumor Response | Progressive Disease | 5 participants |
| Pemetrexed | Overall Tumor Response | Unknown/Unavailable | 11 participants |
Secondary
The 1 and 2 Year Disease-Free Survival Rate (Percentage)
Kaplan-Meier estimates of the percentage of participants still alive at 1-year and 2-years, based upon the total number of participants who had surgery.
Time frame: 1 year and 2 years
Population: All participants who had undergone surgery.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Pemetrexed | The 1 and 2 Year Disease-Free Survival Rate (Percentage) | 1-Year Disease-Free Rate | 61.40 percentage of participants |
| Pemetrexed | The 1 and 2 Year Disease-Free Survival Rate (Percentage) | 2-Year Disease-Free Rate | 33.24 percentage of participants |
Secondary
Time to Progressive Disease
Number of months between the first dose date and the date of first disease progression or death as a result of any cause, whichever comes first.
Time frame: baseline to measured progressive disease
Population: All participants who had undergone surgery.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pemetrexed | Time to Progressive Disease | 14.98 months |
Secondary
Time to Treatment Failure
Time to relapse (treatment failure) is measured in months and calculated as (Date of first surgery - Date of first relapse after surgery + 1)/(365.25/12). Time to relapse will be censored at the date of the last visit or start date of further anti-tumor therapy or intervention, whichever comes first.
Time frame: baseline to stopping treatment
Population: All participants who had undergone surgery.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pemetrexed | Time to Treatment Failure | 18.30 months |