Non-small Cell Lung Cancer
Conditions
Keywords
Dose-Dense Chemotherapy
Brief summary
Dose-dense chemotherapy is a chemotherapy treatment plan in which drugs are given with less time between treatments than in standard chemotherapy. The two chemotherapy drugs used in this study, docetaxel and cisplatin, are approved for the treatment of lung cancer when given every 21 days. This study is exploring the response to chemotherapy when these drugs are given every 14 days. In addition, genetic tests will be performed on pre-treatment specimens to identify signatures that may predict chemotherapy sensitivity or resistance.
Detailed description
All patients will receive induction chemotherapy with cisplatin and docetaxel. Pegfilgrastim will be administered approximately 24 hours following the end of the day 1 chemotherapy infusion. Cycles will be repeated every 2 weeks for 3 cycles. Patients deemed to be resectable will undergo surgical resection followed by postoperative thoracic radiotherapy. Patients deemed inoperable will additionally receive concurrent chemoradiotherapy. Response, using radiographic and/or pathologic means, will identify two cohorts; responders and nonresponders.Gene expression profiling will then be performed on pre-treatment specimens to identify signatures that predict for chemotherapy sensitivity or resistance. The target enrollment is 45 patients.
Interventions
DRUGcisplatin
DRUGDocetaxel
DRUGPegfilgrastim
Sponsors
Sanofi
Duke University
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 with documented stage III NSCLC (IIIA or IIIB, without malignant pleural/pericardial effusion) are eligible for enrollment if they are considered appropriate for treatment with chemotherapy, radiation, or surgery; * IIIA: T1-3 N2 M0, T3 N1 M0 * IIIB: T4 N0-2 M0, T 1-4 N3 M0 * Measurable or evaluable disease * Previously untreated with chemotherapy or radiotherapy for lung cancer; * No brain metastases; * No prior XRT * Performance status 0-2 * ≥18 years of age * Informed Consent * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelets ≥ 100 x 109/L * Bilirubin ≤ 1.5 x upper limit of normal for the institution (ULN) * SGOT and SGPT ≤ 2.5 x ULN for the institution * Creatinine ≤ 1.6 mg/dL * Hemoglobin ≥ 8.0 g/dL * Peripheral neuropathy ≤ grade 1
Exclusion criteria
* Known sensitivity to E. coli derived products (e.g. Filgrastim, HUMULIN® insulin, L-asparaginase, HUMATROPE® Growth Hormone, INTRON® A); * Use of IV systemic antibiotics within 72 hours prior to chemotherapy; * Known HIV infection * Lithium or cytokines within 2 weeks prior of entry * Additional concurrent investigational drugs * History of myelodysplastic syndrome * Pregnant, nursing or having unprotected sex * Not available for follow-up assessment * Unable to comply with protocol procedures * Illnesses that may compromise ability to give informed consent. * Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Response | Between 2 and 3 weeks after induction | Response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Response is defined as the number patients with a Complete Response (CR), disappearance of all target lesions, or a Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. |
| Differential Gene Expression Between Responsive and Resistant Tumor Treated With Dose-dense Therapy | at the end of the study, estimated 2.5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of Grade III/IV Hematologic Adverse Events | During induction chemotherapy, approximately 6 weeks |
| Number of Grade III/IV Non-hematologic Adverse Events | During induction chemotherapy, approximately 6 weeks |
| Number of Patients Who Were Able to Maintain Hemoglobin Between 11-13 g/dL During Induction | During induction, approximately 6 weeks |
| Overall Survival | Approximately 10 years |
Countries
United States
Participant flow
Recruitment details
This study opened to enrollment in May 2006 and closed in October 2009 due to failure to meet accrual goals for data analysis.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects All subjects who signed a consent form are included, whether or not they received treatment as a part of the study. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Failed Screening | 2 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Customized <18 years | 0 years |
| Age, Customized >= 18 years | 13 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 11 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Differential Gene Expression Between Responsive and Resistant Tumor Treated With Dose-dense Therapy
Time frame: at the end of the study, estimated 2.5 years
Population: Due to insufficient accrual, gene analysis was not performed.
Primary
Induction Response
Response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Response is defined as the number patients with a Complete Response (CR), disappearance of all target lesions, or a Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions.
Time frame: Between 2 and 3 weeks after induction
Population: Due to insufficient accrual, data analysis was not performed.
Secondary
Number of Grade III/IV Hematologic Adverse Events
Time frame: During induction chemotherapy, approximately 6 weeks
Population: Due to insufficient accrual, data analysis was not performed.
Secondary
Number of Grade III/IV Non-hematologic Adverse Events
Time frame: During induction chemotherapy, approximately 6 weeks
Population: Due to insufficient accrual, data analysis was not performed.
Secondary
Number of Patients Who Were Able to Maintain Hemoglobin Between 11-13 g/dL During Induction
Time frame: During induction, approximately 6 weeks
Population: Due to insufficient accrual, data analysis was not performed.
Secondary
Overall Survival
Time frame: Approximately 10 years
Population: Due to insufficient accrual, the study was stopped prior to completing the 10 year followup for survival.