Bortezomib, Paclitaxel, and Carboplatin Combined With Radiation Therapy in Treating Patients With Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery - Full Text View

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00093756

Purpose

RATIONALE: 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.

PURPOSE: This phase I/II trial 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.

Condition	Intervention	Phase
Lung Cancer	Drug: bortezomib Drug: carboplatin Drug: paclitaxel Procedure: radiation therapy	Phase I Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Carboplatin Paclitaxel Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I/II Study of PS-341 in Combination With Paclitaxel, Carboplatin, and Concurrent Thoracic Radiation Therapy for Non-Small Cell Lung Cancer (NSCLC)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Proportion of successes [ Designated as safety issue: No ]

Secondary Outcome Measures:

Confirmed tumor response [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Survival time [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	99
Study Start Date:	September 2004
Estimated Primary Completion Date:	August 2005 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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)
Determine the 1-year survival of patients treated with this regimen. (Phase II)

Secondary

Determine the tolerability of this regimen in these patients. (Phase II)
Determine the response rate, progression-free survival, and overall survival of patients treated with this regimen. (Phase II)
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, dose-escalation study of bortezomib, paclitaxel, and carboplatin followed by a phase II study.

Phase I: 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 periodically for up to 5 years from the time of registration.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for the phase I portion of this study within 1.75-2.5 years. A total of 66 patients will be accrued for the phase II portion of this study within 11 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

At least 12 weeks

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 3 times ULN

Renal

Creatinine ≤ 1.5 times ULN

Cardiovascular

No New York Heart Association class III or IV heart disease

Pulmonary

FEV_1 ≥ 1 L OR 35% of predicted

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

No prior systemic chemotherapy for NSCLC* NOTE: *Phase II patients

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy to the chest

Surgery

More than 2 weeks since prior major surgery

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093756

Show 112 Study Locations

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Alex A. Adjei, MD, PhD	Roswell Park Cancer Institute
Investigator:	Steven E. Schild, MD	Mayo Clinic Scottsdale
Investigator:	Jann N. Sarkaria, MD	Mayo Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000390108, NCCTG-N0321
Study First Received:	October 6, 2004
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00093756
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Paclitaxel
Lung Neoplasms
Lung Diseases

Bortezomib
Carboplatin
Carcinoma, Non-Small-Cell Lung
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents

Pharmacologic Actions
Protease Inhibitors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 14, 2009