Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
This study is intended to evaluate the role of paclitaxel poliglumex and carboplatin in the treatment of unresectable Stage III non-small cell lung cancer along with radiation therapy in a multi-institutional trial. Consolidation chemotherapy with paclitaxel poliglumex and carboplatin will follow the completion of chemoradiation.
Interventions
Sponsors
CTI BioPharma
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented NSCLC, including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas). * Eligible Disease Stages: Inoperable IIIA and Selected IIIB * Local radiation oncologist must approve patient eligibility prior to entry on study. * Patients must have measurable disease. * Prior Therapy: * ≥ 2 weeks since formal exploratory thoracotomy. * No prior chemotherapy or radiation therapy for NSCLC. * ECOG performance status 0-1 * Required Initial Laboratory Values (must be submitted within 16 days prior to registration): * Granulocytes ≥ 1,500/µl * Platelets ≥ 100,000/µl * Calculated Creatinine Clearance ≥ 20 cc/min * Bilirubin \< 1.5 mg/dl * AST (SGOT) \< 2 x ULN * INR \> 0.8 \< 1.2\* \*Values apply exclusively to patients not being treated with warfarin. Values for patients being treating with warfarin should fall within the following therapeutic range: \> 2.0 \< 3.0.
Exclusion criteria
* Currently active second malignancy other than non-melanoma skin cancers. Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse. * Pregnant or nursing because of significant risk to the fetus/infant. * Age \<18 years. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * No HIV-positive patients receiving combination anti-retroviral therapy. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy * One-second forced expiratory volume (FEV1) \<50% or hemoglobin-corrected carbon monoxide diffusion capacity (DLCO) \<50% of predicted, as measured within 21 days of study entry * Symptoms of esophageal dysfunction (dysphagia, odynophagia, or inability to swallow solid food) within 4 weeks prior to study randomization. Patients must not require prophylactic placement of percutaneous enterogastrostomy (PEG) tube or other non-oral nutritional supplement methods * Weight loss of \> 10% in the past 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Rate | 6 months | * OS = time from patient registration to death of all causes * Estimated using Kaplan Meier |
| Overall Survival (OS) | Completion of follow-up (follow-up ranged from 3 months to 6 years) | OS = time from patient registration to death of all causes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates | 4 years | Overall best response using RECIST 1.0 |
| Failure-free Survival (FFS) Rate | 6 months | * The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first) * Estimated using Kaplan Meier |
| Incidence and Severity of Radiation-induced Pneumonitis | 30 days following completion of treatment (approximately 114 days) | — |
| Incidence and Severity of Radiation-induced Esophagitis | 30 days following completion of treatment (approximately 114 days) | — |
| Failure-free Survival (FFS) | Completion of follow-up (follow-up ranged from 3 months to 6 years) | The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first) |
Countries
United States
Participant flow
Recruitment details
Enrollment to the study was opened on 04/05/2006 and enrollment to the study closed 06/30/2008.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (First 12 Eligible Patients) Paclitaxel poliglumex 135 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles.
Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles.
Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions.
Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.
Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. | 8 |
| Cohort 2 (Remaining Patients) Paclitaxel poliglumex 175 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles.
Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles.
Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions.
Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.
Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. | 0 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Determined to be ineligible | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 (First 12 Eligible Patients) | Total |
|---|---|---|
| Age, Continuous | 69 years | 69 years |
| Gender Female | 5 Participants | — |
| Gender Male | 3 Participants | — |
| Region of Enrollment United States | 8 participants | 8 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 0 / 0 |
| serious Total, serious adverse events | 5 / 8 | 0 / 0 |
Outcome results
Primary
Overall Survival (OS)
OS = time from patient registration to death of all causes
Time frame: Completion of follow-up (follow-up ranged from 3 months to 6 years)
Population: Participants with unknown expiration dates were censored at the date of last clinical contact.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (First 12 Eligible Patients) | Overall Survival (OS) | 10.4 months |
Primary
Overall Survival (OS) Rate
* OS = time from patient registration to death of all causes * Estimated using Kaplan Meier
Time frame: 6 months
Population: Participants with unknown expiration dates were censored at the date of last clinical contact.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (First 12 Eligible Patients) | Overall Survival (OS) Rate | 73 percentage of participants |
Secondary
Failure-free Survival (FFS)
The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first)
Time frame: Completion of follow-up (follow-up ranged from 3 months to 6 years)
Population: Participants with unknown event dates were censored at the date of last clinical contact.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (First 12 Eligible Patients) | Failure-free Survival (FFS) | 6 months |
Secondary
Failure-free Survival (FFS) Rate
* The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first) * Estimated using Kaplan Meier
Time frame: 6 months
Population: Participants with unknown event dates were censored at the date of last clinical contact.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (First 12 Eligible Patients) | Failure-free Survival (FFS) Rate | 44 percentage of participants |
Secondary
Incidence and Severity of Radiation-induced Esophagitis
Time frame: 30 days following completion of treatment (approximately 114 days)
Population: Using CTCAE Version 3.0
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Esophagitis | Grade 1 | 1 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Esophagitis | Grade 2 | 3 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Esophagitis | Grade 3 | 0 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Esophagitis | Grade 4 | 0 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Esophagitis | Grade 5 | 0 participants |
Secondary
Incidence and Severity of Radiation-induced Pneumonitis
Time frame: 30 days following completion of treatment (approximately 114 days)
Population: Using CTCAE Version 3.0.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Pneumonitis | Grade 1 | 1 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Pneumonitis | Grade 2 | 2 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Pneumonitis | Grade 3 | 1 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Pneumonitis | Grade 4 | 0 participants |
| Cohort 1 (First 12 Eligible Patients) | Incidence and Severity of Radiation-induced Pneumonitis | Grade 5 | 0 participants |
Secondary
Response Rates
Overall best response using RECIST 1.0
Time frame: 4 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (First 12 Eligible Patients) | Response Rates | Complete response | 1 participants |
| Cohort 1 (First 12 Eligible Patients) | Response Rates | Partial response | 5 participants |
| Cohort 1 (First 12 Eligible Patients) | Response Rates | Progressive disease | 1 participants |
| Cohort 1 (First 12 Eligible Patients) | Response Rates | Unknown | 1 participants |