Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC
- Conditions
- Lung Cancer
- Interventions
- Registration Number
- NCT00544648
- Lead Sponsor
- Vanderbilt-Ingram Cancer Center
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) may make tumor cells more sensitive to radiation therapy. Giving nab-paclitaxel together with radiation therapy and carboplatin may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving nab-paclitaxel together with carboplatin and radiation therapy and to see how well it works in treating patients with stage III non-small-cell lung cancer that cannot be removed by surgery.
- Detailed Description
OBJECTIVES:
Primary
* To determine the maximum tolerated dose of nab-paclitaxel when combined concurrently with carboplatin and radiation followed by two courses of nab-paclitaxel carboplatin as consolidation. (Phase I)
* To evaluate the progression-free survival in patients with stage III unresectable non-small cell lung cancer treated with nab-paclitaxel, carboplatin, and radiotherapy followed by two courses of nab-paclitaxel with carboplatin as consolidation. (Phase II)
Secondary
* To assess safety and tolerability and identify dose-limiting toxicities in patients receiving nab-paclitaxel combined concurrently with carboplatin and radiotherapy. (Phase I)
* To assess progression-free survival, response rates, and survival. (Phase I)
* To assess overall survival and response rates in all patients treated on this study. (Phase II)
* To assess the safety and tolerability of patients receiving nab-paclitaxel combined concurrently with carboplatin and radiotherapy followed by two courses of nab-paclitaxel/carboplatin as consolidation. (Phase II) OUTLINE: This is a multicenter study.
* Phase I:
* Concurrent chemoradiotherapy: Patients receive escalating doses of nab-paclitaxel IV over 30 minutes and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43. They also receive conformal radiotherapy once daily 5 days a week on days 1-5 in weeks 1-7. Patients are evaluated between weeks 8-10. Patients with disease progression are removed from study. Patients with stable disease, partial response, or complete response proceed to consolidation chemotherapy 3 weeks after completion of chemoradiotherapy.
* Consolidation chemotherapy: Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats ever 21 days for up to 2 courses.
* Phase II: Patients receive concurrent chemoradiotherapy at the Maximum Tolerated Dose (MTD) of nab-paclitaxel followed by consolidation chemotherapy as in phase I.
After completion of study treatment, patients are followed at 2 months, every 3 months for 2 years, every 4 months for 2 years, and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 98 patients (15 patients for phase I and 83 patients for phase II) will be accrued for this study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 13
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment nab-paclitaxel nab-paclitaxel+ carboplatin + radiation Treatment Radiation therapy nab-paclitaxel+ carboplatin + radiation Treatment carboplatin nab-paclitaxel+ carboplatin + radiation
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I) 7 weeks The highest dose in milligrams per meter of body surface squared (mg/m2) of nab-paclitaxel in combination with carboplatin while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of nab-paclitaxel in combination with carboplatin until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs per Common Toxicity Criteria v 3.0: recurring non-hematological (except esophagitis) \> Grade 2, non-hematological or esophagitis \> Grade 3 toxicities that are symptomatically unacceptable to patient and result in treatment delay for \> 2 weeks, persistent toxicity resulting in treatment delay for \> 2 weeks.
Progression-free Survival (Phase II) On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years) Estimated probable duration of life without disease progression, from on-study date to earlier of progression date, or date of death from any cause, using the Kaplan-Meier method with censoring (see Analysis Population Description for additional details). Disease progression is defined by Response Evaluation in Solid Tumors (RECIST) v.1.1: \>= 20% increase in sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions
- Secondary Outcome Measures
Name Time Method Progression-free Survival (Phase I) On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years) Estimated probable duration of life without disease progression, from on-study date to earlier of progression date, or date of death from any cause, using the Kaplan-Meier method with censoring (see Analysis Population Description for additional details). Disease progression is defined by Response Evaluation in Solid Tumors (RECIST) v.1.1: \>= 20% increase in sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions
Overall Survival (Phase I) On-study date to date of death from any cause (assessed up to 2 years) Estimated probable duration of life from on-study date to date of death from any cause, using Kaplan-Meier method with censoring (see Analysis Population Description for additional details).
Response (Phase I) On-treatment date to date of progressive disease (assessed up to 2 years) Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) \>=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.
Number of Patients With Each Worst Grade Toxicity (Phase I) On-study date to 30 days following final dose of study drug Count of patients according to the worst-grade toxicity (WGT) experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening; Grade 5, death.
Overall Survival (Phase II) Time Frame: date on study to date of death from any cause or last known date alive Estimated probable duration of life from on-study date to date of death from any cause, using Kaplan-Meier method with censoring (see Analysis Population Description for additional details. Too few patients were enrolled in the Phase II arm for an analysis of overall survival
Number of Patients With Each Worst Grade Toxicity (Phase II) at 16 weeks The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death
Response (Phase II) On-treatment date to date of progressive disease (assessed up to 2 years) Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) \>=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.
Trial Locations
- Locations (6)
Vanderbilt-Ingram Cancer Center at Franklin
🇺🇸Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Purchase Cancer Group - Paducah
🇺🇸Paducah, Kentucky, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
Vanderbilt-Ingram Cancer Center - Cool Springs
🇺🇸Nashville, Tennessee, United States
Erlanger Cancer Center at Erlanger Hospital - Baroness
🇺🇸Chattanooga, Tennessee, United States