Non-Small Cell Lung Cancer
Conditions
Keywords
Stage IIIB/IV
Brief summary
This is an open-label, single institution, phase II study of Sorafenib in combination with docetaxel and carboplatin in patients with advanced non-small cell lung cancer. Docetaxel and carboplatin will be given on day 1 of every three week cycle. Patients will take Sorafenib twice a day on the 1st day of treatment and continue to take the medication every day until progression of disease, prohibitive toxicity, or patient withdrawal from the study. Chemotherapy courses will repeat every 21 days in the absence of disease progression or unacceptable toxicity for a total of four cycles.
Detailed description
Patients will be monitored after every two cycles (6 weeks) for tumor response, stability, or progression by radiographic imaging studies. The primary goal of this study is to determine the clinical response rate of this regimen in patients with advanced lung cancer. Secondary endpoints include time to progression, overall survival, and toxicity. Blood levels of ERK-phosphorylation, activated caspase 3, cyclin D1, anti -cIAP2, p-Akt, and Mcl1 activity will be measured at the beginning, middle and end of therapy to help identify predictors of drug response and toxicity during the first cycle of treatment.
Interventions
DRUGSorafenib + Docetaxel/Carboplatin
400 mg po BID Sorafenib + 75 mg/m2 IV Docetaxel on day 1 plus AUC 6 on Carboplatin on day 1 of each 21 day cycle
Sponsors
Abramson Cancer Center at Penn Medicine
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
* Histologically or cytologically confirmed NSCLC with clinical or radiological evidence of advanced disease (Stage IIIB/IV) * Uni-dimensionally measurable disease * Age =\> 18 years * ECOG performance status of 0-1 * Life expectancy \> 3 months
Exclusion criteria
* Small-cell or mixed histologies including a small cell component * Prior chemotherapy, biotherapy, radiotherapy to an area of measurable disease * Patients with peripheral neuropathy grade =\> 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With Stage IIIB/IV NSCLC Response Rate to the Combination Therapy of Sorafenib and Docetaxel/Carboplatin | 30 months | The response rate from the combination therapy of Sorafenib and Docetaxel/carboplatin for patients with Stage IIIB/IV NSCLC.The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria (see section 9.3.1).Tumor Response: Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): a) At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): a) At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants the Progression-free Survival (PFS) . | 30 months | Disease progression is based on RECIST documentation. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions |
| Number of Participants With Serious Adverse Events | 30 months | Assessment of adverse events related to the combination infusion, These include a Serious Adverse Event (SAE) is an adverse event occurring at any dose that results in any of the following outcomes: 1. Death 2. Life-threatening 3. Persistent or significant disability/incapacity 4. In patient hospitalization or prolongation of existing hospitalization 5. Congenital anomaly/birth defect or • blood dyscrasia without inpatient hospitalization * convulsions without inpatient hospitalization * intensive treatment in an emergency room or at home for allergic bronchospasm without inpatient hospitalization * development of drug dependency * drug abuse * overdose with an associated serious event, or required intervention to prevent impairment/damage |
| The Number of Participants With Biomarkers of Sorafenib Activity and Toxicity | 30 months | Monitored at designated timepoints.All patients will be evaluable for toxicity from the time of their first treatment with SORAFENIB. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sorafinb + Docetoxel+Carboplatin 400 mg po BID Sorafenib + 75 mg/m2 IV Docetaxel on day 1 plus AUC 6 on Carboplatin on day 1 of each 21 day cycle
Sorafenib + Docetaxel/Carboplatin: 400 mg po BID Sorafenib + 75 mg/m2 IV Docetaxel on day 1 plus AUC 6 on Carboplatin on day 1 of each 21 day cycle | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Sorafinb + Docetoxel+Carboplatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
The Number of Patients With Stage IIIB/IV NSCLC Response Rate to the Combination Therapy of Sorafenib and Docetaxel/Carboplatin
The response rate from the combination therapy of Sorafenib and Docetaxel/carboplatin for patients with Stage IIIB/IV NSCLC.The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria (see section 9.3.1).Tumor Response: Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): a) At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): a) At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: 30 months
Population: Sufficient data was not collected.
Secondary
Number of Participants the Progression-free Survival (PFS) .
Disease progression is based on RECIST documentation. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
Time frame: 30 months
Population: Sufficient data was not collected.
Secondary
Number of Participants With Serious Adverse Events
Assessment of adverse events related to the combination infusion, These include a Serious Adverse Event (SAE) is an adverse event occurring at any dose that results in any of the following outcomes: 1. Death 2. Life-threatening 3. Persistent or significant disability/incapacity 4. In patient hospitalization or prolongation of existing hospitalization 5. Congenital anomaly/birth defect or • blood dyscrasia without inpatient hospitalization * convulsions without inpatient hospitalization * intensive treatment in an emergency room or at home for allergic bronchospasm without inpatient hospitalization * development of drug dependency * drug abuse * overdose with an associated serious event, or required intervention to prevent impairment/damage
Time frame: 30 months
Population: Sufficient data was not collected.
Secondary
The Number of Participants With Biomarkers of Sorafenib Activity and Toxicity
Monitored at designated timepoints.All patients will be evaluable for toxicity from the time of their first treatment with SORAFENIB.
Time frame: 30 months
Population: Sufficient data was not collected.