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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00093756
First received: October 6, 2004
Last updated: October 7, 2013
Last verified: October 2013

October 6, 2004
October 7, 2013
September 2004
January 2012   (final data collection date for primary outcome measure)
Proportion of successes, defined as the number of patients alive at one year divided by the total number of evaluable patients [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Not Provided
Complete list of historical versions of study NCT00093756 on ClinicalTrials.gov Archive Site
  • Confirmed tumor response, defined as a complete or partial response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: From study registration to date of disease progression or date of last follow-up, up to 5 years ] [ Designated as safety issue: No ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.
  • Progression-free survival [ Time Frame: From study registration to the first of either death due to any cause or progression, up to 5 years ] [ Designated as safety issue: No ]
    The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
  • Survival time [ Time Frame: From registration to death due to any cause, up to 5 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
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
Phase I/II Study of PS-341 in Combination With Paclitaxel, Carboplatin, and Concurrent Thoracic Radiation Therapy for Non-small Cell Lung Cancer (NSCLC)

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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Non-small Cell Lung Cancer
  • Stage IIIA Non-small Cell Lung Cancer
  • Stage IIIB Non-small Cell Lung Cancer
  • Radiation: 3-dimensional conformal radiation therapy
  • Drug: bortezomib
    Given IV
  • Drug: paclitaxel
    Given IV
  • Drug: carboplatin
    Given IV
Experimental: Treatment (radiation, bortezomib, paclitaxel, carboplatin)
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. PHASE II: Patients receive bortezomib, paclitaxel, and carboplatin as in phase I at the MTD. Patients also undergo radiotherapy as in phase I.
Interventions:
  • Radiation: 3-dimensional conformal radiation therapy
  • Drug: bortezomib
  • Drug: paclitaxel
  • Drug: carboplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
99
Not Provided
January 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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 - 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)
  • AST ≤ 3 times ULN
  • Creatinine ≤ 1.5 times ULN
  • No New York Heart Association class III or IV heart disease
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00093756
NCI-2009-00643, NCI-2009-00643, CDR0000390108, NCCTG-N0321, N0321, N0321, U10CA025224
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Alex Adjei North Central Cancer Treatment Group
National Cancer Institute (NCI)
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP