Non-Small Cell Lung Cancer
Conditions
Keywords
Advanced Non-Small Cell Lung Cancer
Brief summary
The primary objective of this trial is to compare the survival of patients with advanced non-small cell lung cancer (NSCLC) treated with weekly Taxoprexin in combination with carboplatin to those treated with paclitaxel plus carboplatin in a prospectively randomized trial. In addition, the response rate to each regimen, response duration, time to progression and time to treatment failure will be measured. Toxicity will be evaluated and compared between the two groups.
Detailed description
This is a randomized, multicenter, Phase III open-label study of weekly Taxoprexin® in combination with every three (3) week carboplatin compared to paclitaxel plus carboplatin every three (3) weeks, in patients with advanced non-small cell lung cancer (NSCLC) who have not received cytotoxic agents for advanced disease. Patients may have been previously treated with immunological agents. Patients will be randomized to receive Taxoprexin® at a dose of 400 mg/m2 intravenously by one (1)-hour weekly infusion, 5/6 weeks followed immediately by carboplatin AUC = 4 on weeks one (1) and four (4) as a 30 minute intravenous infusion or paclitaxel 225mg/m2 as a three (3) hour intravenous infusion followed immediately by carboplatin AUC = 6 as a 30 minute intravenous infusion, every three (3) weeks. Patients will receive Taxoprexin® and carboplatin infusions or paclitaxel and carboplatin infusions until progression of disease, intolerable toxicity, completion of six (6) treatment cycles of paclitaxel plus carboplatin or three (3) treatment cycles of Taxoprexin® plus carboplatin, refusal of continued treatment by the patient, or Investigator decision.
Interventions
DRUGTaxoprexin
Administered by intravenous infusion over 1 hour infusion
DRUGCarboplatin
Administered by intravenous infusion over 30 minutes. Dosing was based on the Calvert formula: carboplatin dose (mg) = (Target AUC) x (glomerular filtration rate (GFR) + 25).
DRUGPaclitaxel
Administered by intravenous infusion over 3 hour infusion
Sponsors
American Regent, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have a histologic or cytologic diagnosis of non-small cell lung cancer. At the time of study entry, patients must have locally advanced (stage IIIb) or metastatic (stage IV) disease. 2. Patients must have at least one site of either measurable or non-measurable disease. 3. Patients must not have received prior systemic chemotherapy for metastatic disease. Prior adjuvant systemic chemotherapy is allowed. At least six (6) months must have elapsed since any prior adjuvant systemic chemotherapy. 4. At least 6 weeks (42 days) since any prior immunotherapy, cytokine, biologic, vaccine or other non chemotherapy anticancer systemic therapies, unless patients have progressed during or after such therapy. 5. At least 4 weeks (28 days) since any prior radiotherapy to \> 25% of the bone marrow. 6. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2. 7. Patients must be at least 18 years of age. 8. Patients must have adequate hepatic and renal function. 9. Patients must have adequate bone marrow function. 10. Life expectancy of at least 3 months. 11. Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study and in keeping with the policies of their institution.
Exclusion criteria
1. Patients who have received prior systemic chemotherapy in the adjuvant setting with a treatment-free interval of less than six (6) months. 2. Patients who have a past or current history of neoplasms other than the entry diagnosis, except for curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix and except for other cancers treated for cure and with a disease-free survival greater than 5 years. 3. Patients with symptomatic brain metastasis(es). 4. Women who are pregnant or nursing and men or women who are not practicing an acceptable method of birth control. Women may not breast-feed while on this study. 5. Patients with current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals). 6. Patients with current peripheral neuropathy of any etiology that is greater than grade 1. 7. Patients with unstable or serious concurrent medical conditions. 8. Patients with a known hypersensitivity to Cremophor. 9. Patients with Gilbert's syndrome. 10. Patients must not have had major surgery within the past 14 days. 11. Patients must not receive any concurrent chemotherapy, radiotherapy, or immunotherapy while on study. 12. No known HIV disease or infection. 13. Patients receiving ketoconazole, erythromycin, verapamil, diazepam, quinidine, or diltiazem.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 12 months | Overall survival was defined as the time from the day of randomization and ends at death of the participant. Participants were followed every 2 months, whether on or off study, for survival information. Participants alive at the time of termination of the study were considered censored. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an Objective Complete Response or Partial Response | Assessed every 6 weeks, up to 12 months | Antitumor response was defined as the percentage of participants who achieved an objective response (Complete Response or Partial Response), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0. A complete response was defined as a disappearance of all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial response was defined as a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum of LD determined by 2 consecutive observations not less than 4 weeks apart. |
| Duration of Response | Assessed every 6 weeks, up to 12 months | Duration of overall response was a measurement from the time measure criteria was met for confirmed complete response or partial response (whichever was first recorded) until the first date that recurrent of progressive disease was objectively documented (taking as reference for progressive disease the smallest measurement recorded since treatment started). |
| Time to Progression (TTP) | Up to 12 months | TTP was defined as the time from randomization to documented disease progression. Progressive disease was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as references the smallest sum LD recorded since treatment start or the appearance of 1 or more lesions. |
| Time to Treatment Failure (TTF) | Baseline to stopping treatment, up to 12 months | TTF is defined as the time from randomization to the discontinuation of protocol treatment for any reason |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Taxoprexin® and Carboplatin Taxoprexin® 400 mg/m² intravenously weekly for 5 weeks
Carboplatin was given at an Area Under the Curve (AUC) = 4 mg\*min/mL on Week 1 and Week 4, Taxoprexin and carboplatin were given up to 3 treatment cycles.
Taxoprexin: Administered by intravenous infusion over 1 hour infusion
Carboplatin: Administered by intravenous infusion over 30 minutes. Dosing was based on the Calvert formula: carboplatin dose (mg) = (Target AUC) x (glomerular filtration rate \[GFR\] + 25). | 260 |
| Paclitaxel and Carboplatin Paclitaxel 225 mg/m² intravenously followed immediately by carboplatin AUC = 6 mg\*min/mL. Paclitaxel and carboplatin were given up to 6 treatment cycles.
Carboplatin: Administered by intravenous infusion over 30 minutes. Dosing was based on the Calvert formula: carboplatin dose (mg) = (Target AUC) x (glomerular filtration rate \[GFR\] + 25).
Paclitaxel: Administered by intravenous infusion over 3 hour infusion | 258 |
| Total | 518 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 24 | 34 |
| Overall Study | Delayed treatment, omission of treatment, peripheral neuropathy, intercurrent illness | 22 | 31 |
| Overall Study | Lack of Efficacy | 115 | 78 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 2 | 7 |
| Overall Study | Withdrawal by Subject | 11 | 23 |
Baseline characteristics
| Characteristic | Taxoprexin® and Carboplatin | Paclitaxel and Carboplatin | Total |
|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 9.35 | 62.4 years STANDARD_DEVIATION 10.54 | 62.8 years STANDARD_DEVIATION 9.96 |
| Disease Stage IIIb | 57 Participants | 53 Participants | 110 Participants |
| Disease Stage IV | 203 Participants | 205 Participants | 408 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 13 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 249 Participants | 244 Participants | 493 Participants |
| Region of Enrollment Russia | 50 Participants | 49 Participants | 99 Participants |
| Region of Enrollment Ukraine | 49 Participants | 46 Participants | 95 Participants |
| Region of Enrollment United States | 161 Participants | 163 Participants | 324 Participants |
| Sex: Female, Male Female | 81 Participants | 68 Participants | 149 Participants |
| Sex: Female, Male Male | 179 Participants | 190 Participants | 369 Participants |
| Weight | 73.88 kilograms STANDARD_DEVIATION 15.111 | 75.46 kilograms STANDARD_DEVIATION 17.567 | 74.67 kilograms STANDARD_DEVIATION 16.378 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 198 / 256 | 196 / 251 |
| other Total, other adverse events | 235 / 256 | 239 / 251 |
| serious Total, serious adverse events | 70 / 256 | 91 / 251 |
Outcome results
Primary
Overall Survival
Overall survival was defined as the time from the day of randomization and ends at death of the participant. Participants were followed every 2 months, whether on or off study, for survival information. Participants alive at the time of termination of the study were considered censored.
Time frame: Up to 12 months
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Taxoprexin® and Carboplatin | Overall Survival | 8.31 Months |
| Paclitaxel and Carboplatin | Overall Survival | 8.51 Months |
Secondary
Duration of Response
Duration of overall response was a measurement from the time measure criteria was met for confirmed complete response or partial response (whichever was first recorded) until the first date that recurrent of progressive disease was objectively documented (taking as reference for progressive disease the smallest measurement recorded since treatment started).
Time frame: Assessed every 6 weeks, up to 12 months
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Taxoprexin® and Carboplatin | Duration of Response | 5.75 Months |
| Paclitaxel and Carboplatin | Duration of Response | 5.35 Months |
Secondary
Percentage of Participants Who Achieved an Objective Complete Response or Partial Response
Antitumor response was defined as the percentage of participants who achieved an objective response (Complete Response or Partial Response), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0. A complete response was defined as a disappearance of all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial response was defined as a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum of LD determined by 2 consecutive observations not less than 4 weeks apart.
Time frame: Assessed every 6 weeks, up to 12 months
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Taxoprexin® and Carboplatin | Percentage of Participants Who Achieved an Objective Complete Response or Partial Response | 40 Participants |
| Paclitaxel and Carboplatin | Percentage of Participants Who Achieved an Objective Complete Response or Partial Response | 95 Participants |
Secondary
Time to Progression (TTP)
TTP was defined as the time from randomization to documented disease progression. Progressive disease was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as references the smallest sum LD recorded since treatment start or the appearance of 1 or more lesions.
Time frame: Up to 12 months
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Taxoprexin® and Carboplatin | Time to Progression (TTP) | 3.02 Months |
| Paclitaxel and Carboplatin | Time to Progression (TTP) | 4.47 Months |
Secondary
Time to Treatment Failure (TTF)
TTF is defined as the time from randomization to the discontinuation of protocol treatment for any reason
Time frame: Baseline to stopping treatment, up to 12 months
Population: Intent to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Taxoprexin® and Carboplatin | Time to Treatment Failure (TTF) | 2.79 Months |
| Paclitaxel and Carboplatin | Time to Treatment Failure (TTF) | 3.25 Months |