Bortezomib, Paclitaxel, Carboplatin and Radiation Therapy for Non-Small Cell Lung Cancer
- Conditions
- Stage IIIB Non-small Cell Lung CancerRecurrent Non-small Cell Lung CancerStage IIIA Non-small Cell Lung Cancer
- Interventions
- Radiation: 3-dimensional conformal radiation therapy
- Registration Number
- NCT00093756
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase I/II trial (phase I closed to accrual as of 09/29/2009) is studying the side effects and best dose of bortezomib, paclitaxel, and carboplatin when given with radiation therapy and to see how well they work in treating patients with stage IIIA or stage IIIB non-small cell lung cancer that cannot be removed by surgery. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may increase the effectiveness of paclitaxel and carboplatin by making tumor cells more sensitive to the drugs. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving bortezomib, paclitaxel, and carboplatin together with radiation therapy may kill more tumor cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of bortezomib, paclitaxel, and carboplatin when administered with fractionated radiotherapy in patients with unresectable stage IIIA or IIIB non-small cell lung cancer. (Phase I) (closed to accrual as of 09/29/2009) II. Determine the 1-year survival of patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the tolerability of this regimen in these patients. (Phase II) II. Determine the response rate, progression-free survival, and overall survival of patients treated with this regimen. (Phase II) III. Correlate p27 expression in tumor tissue with survival, time to progression, and response in patients treated with this regimen. (Phase II)
OUTLINE: This is a multicenter, phase I (closed to accrual as of 09/29/2009), dose-escalation study of bortezomib, paclitaxel, and carboplatin followed by a phase II study.
PHASE I: (closed to accrual as of 09/29/2009) Patients receive bortezomib IV on days 1, 4, 8, and 11. Patients also receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 2. Patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19. Treatment repeats every 3 weeks up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib, paclitaxel, and carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive bortezomib, paclitaxel, and carboplatin as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. Patients are followed up periodically for up to 5 years from the time of registration.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
- Locally advanced stage IIIA or IIIB disease that is considered unresectable
- No stage IV disease
- Requires radiotherapy
- Performance status (PS) - Eastern Cooperative Oncology Group (ECOG) 0-1
- At least 12 weeks
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- aspartate aminotransferase (AST) ≤ 3 times ULN
- Creatinine ≤ 1.5 times ULN
- No New York Heart Association class III or IV heart disease
- Forced expiratory volume (FEV) FEV_1 ≥ 1 L OR 35% of predicted
- Weight loss < 10% within the past 3 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No peripheral neuropathy ≥ grade 2
- No other severe underlying disease that would preclude study participation
- No uncontrolled infection
- No unhealed wound within the past 2 weeks
- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas (carcinoma in situ), or localized prostate cancer
- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
- No prior systemic chemotherapy for NSCLC*
- No prior radiotherapy to the chest
- More than 2 weeks since prior major surgery
Contraindications
-
Any of the following:
- Pregnant wome
- Nursing women
- Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.) as this regimen may be harmful to a developing fetus or nursing child NOTE: This study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
-
Any of the following prior therapies:
- Prior radiation therapy to the chest
- Prior systemic chemotherapy for NSCLC (phase II portion)
-
New York Heart Association classification III or IV (see Appendix II).
-
Any other severe underlying diseases which are, in the judgment of the investigator, inappropriate for entry into this study.
-
uncontrolled infection.
-
Major surgery or unhealed wound ≤ 2 weeks prior to registration.
-
Prior history of malignancy ≤ 5 years, except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas (carcinoma in situ), or localized prostate cancer.
-
Peripheral neuropathy ≥grade 2
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (bortezomib, paclitaxel, carboplatin) 3-dimensional conformal radiation therapy PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy bortezomib: Given IV paclitaxel: Given IV carboplatin: Given IV Treatment (bortezomib, paclitaxel, carboplatin) bortezomib PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy bortezomib: Given IV paclitaxel: Given IV carboplatin: Given IV Treatment (bortezomib, paclitaxel, carboplatin) carboplatin PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy bortezomib: Given IV paclitaxel: Given IV carboplatin: Given IV Treatment (bortezomib, paclitaxel, carboplatin) paclitaxel PHASE I: Cohorts of 3-6 patients receive escalating doses of study medications until the maximum tolerated dose (MTD) is determined. PHASE II: Patients receive as in phase I at the MTD. Patients also undergo radiotherapy as in phase I. 3-dimensional conformal radiation therapy bortezomib: Given IV paclitaxel: Given IV carboplatin: Given IV
- Primary Outcome Measures
Name Time Method The Primary Endpoint of This Trial is the Proportion of Patients Alive at 1 Year. Phase II Patients Only. At 1 year The primary endpoint of this trial is the proportion of patients alive at 1 year (i.e., 365 days) after study registration. Proportion of successes, defined as the number of patients alive at one year divided by the total number of evaluable patients.
- Secondary Outcome Measures
Name Time Method Confirmed Tumor Response Up to 5 years Response was assessed using the RECIST v1.1 criteria. Patients were evaluated at 4 weeks post-RT, 3 months post-RT, every 3 months for 1 year post-RT, and every 6 months thereafter for a maximum of 5 years from time of registration. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 20% decrease in the sum of the longest diameter of target lesions from baseline. A confirmed response is defined as a CR or PR as the objective status on 2 consecutive evaluations at least 4 weeks apart.
Time to Progression From study registration to date of disease progression or date of last follow-up, up to 5 years The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Progression-free Survival From study registration to the first of either death due to any cause or progression, up to 5 years The distribution of progression-free survival (PFS) is defined as the time from registration to the time of progression or death, whichever comes first. The PFS will be estimated using the method of Kaplan-Meier.
Overall Survival From registration to death due to any cause, up to 5 years Overall Survival is defined as the time from registration to the time to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Frequency and Severity of Observed Toxicity, Graded by Common Terminology Criteria for Adverse Events (CTCAE) Up to 5 years Toxicity was reported after the first 21 days of treatment and after each 28 day cycle thereafter. Events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. The number of patients reporting grade 3 and higher are tabulated.
Trial Locations
- Locations (142)
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Carle Foundation - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Siouxland Regional Cancer Center
🇺🇸Sioux City, Iowa, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Metro-Minnesota CCOP
🇺🇸Saint Louis Park, Minnesota, United States
Altru Cancer Center
🇺🇸Grand Forks, North Dakota, United States
Geisinger Wyoming Valley
🇺🇸Wilkes-Barre, Pennsylvania, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Cancer Center of Kansas - Main Office
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Saint Alexius Medical Center
🇺🇸Bismarck, North Dakota, United States
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Mercy Capitol
🇺🇸Des Moines, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Kewanee Hospital
🇺🇸Kewanee, Illinois, United States
Joliet Oncology-Hematology Associates Limited
🇺🇸Joliet, Illinois, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Saint Francis Hospital and Medical Center
🇺🇸Hartford, Connecticut, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Illinois CancerCare-Havana
🇺🇸Havana, Illinois, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Holy Family Medical Center
🇺🇸Monmouth, Illinois, United States
Illinois CancerCare-Community Cancer Center
🇺🇸Normal, Illinois, United States
Illinois CancerCare-Monmouth
🇺🇸Monmouth, Illinois, United States
Community Cancer Center Foundation
🇺🇸Normal, Illinois, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸El Dorado, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Hospital District Sixth of Harper County
🇺🇸Anthony, Kansas, United States
Associates In Womens Health
🇺🇸Wichita, Kansas, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Oakwood Hospital
🇺🇸Dearborn, Michigan, United States
OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC
🇺🇸Peoria, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Saint Luke's Hospital
🇺🇸Cedar Rapids, Iowa, United States
Valley Cancer Center
🇺🇸Spring Valley, Illinois, United States
Cancer Center of Kansas - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Siouxland Hematology Oncology Associates
🇺🇸Sioux City, Iowa, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸Flint, Michigan, United States
Cancer Center of Kansas - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸Kingman, Kansas, United States
Wichita CCOP
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸Liberal, Kansas, United States
Essentia Health Duluth Clinic CCOP
🇺🇸Duluth, Minnesota, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Saint Mary's of Michigan
🇺🇸Saginaw, Michigan, United States
Fairview-Southdale Hospital
🇺🇸Edina, Minnesota, United States
Essentia Health Saint Mary's Medical Center
🇺🇸Duluth, Minnesota, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸Livonia, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸Port Huron, Michigan, United States
Bismarck Cancer Center
🇺🇸Bismarck, North Dakota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Essentia Health Saint Joseph's Medical Center
🇺🇸Brainerd, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Adult and Pediatric Urology PLLP
🇺🇸Sartell, Minnesota, United States
Minnesota Oncology and Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
Meeker County Memorial Hospital
🇺🇸Litchfield, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Saint Joseph's Hospital - Healtheast
🇺🇸Saint Paul, Minnesota, United States
Rutherford Hospital
🇺🇸Rutherfordton, North Carolina, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Woodwinds Health Campus
🇺🇸Woodbury, Minnesota, United States
Mid Dakota Clinic
🇺🇸Bismarck, North Dakota, United States
Upstate Carolina CCOP
🇺🇸Spartanburg, South Carolina, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
Saint Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Oncology Associates at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸Ann Arbor, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Mercy Medical Center-Sioux City
🇺🇸Sioux City, Iowa, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Spring Valley
🇺🇸Spring Valley, Illinois, United States
Carle Clinic-Urbana Main
🇺🇸Urbana, Illinois, United States
Saint Anthony Memorial Health Center
🇺🇸Michigan City, Indiana, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸Clive, Iowa, United States
Saint Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Geisinger Medical Group
🇺🇸State College, Pennsylvania, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Saint Anthony Memorial Hospital
🇺🇸Effingham, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸Galesburg, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Hopedale Medical Complex - Hospital
🇺🇸Hopedale, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Pekin Hospital
🇺🇸Pekin, Illinois, United States
Cedar Rapids Oncology Association
🇺🇸Cedar Rapids, Iowa, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Geisinger Medical Center-Cancer Center Hazelton
🇺🇸Hazleton, Pennsylvania, United States
AnMed Health Hospital
🇺🇸Anderson, South Carolina, United States
Iowa Oncology Research Association CCOP
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates
🇺🇸Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Cancer Center of Kansas - Winfield
🇺🇸Winfield, Kansas, United States
Harris, John Gilbert MD (UIA Investigator)
🇺🇸Alexandria, Minnesota, United States
Brainerd Medical Center Inc
🇺🇸Brainerd, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Cancer Center of Kansas - Parsons
🇺🇸Parsons, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸Pratt, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸Wellington, Kansas, United States