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Bortezomib, Paclitaxel, Carboplatin and Radiation Therapy for Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00093756
First Posted: October 8, 2004
Last Update Posted: December 8, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
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.

Condition Intervention Phase
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 Drug: paclitaxel Drug: carboplatin Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: 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)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The Primary Endpoint of This Trial is the Proportion of Patients Alive at 1 Year. Phase II Patients Only. [ Time Frame: 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:
  • 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 ]
  • Time to Progression [ Time Frame: 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 [ Time Frame: 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 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 ]
    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 ]

Enrollment: 52
Study Start Date: September 2004
Study Completion Date: May 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib, paclitaxel, 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

Radiation: 3-dimensional conformal radiation therapy Drug: bortezomib
Given IV
Drug: paclitaxel
Given IV
Drug: carboplatin
Given IV

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00093756


  Show 143 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Alex Adjei North Central Cancer Treatment Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00093756     History of Changes
Other Study ID Numbers: NCI-2009-00643
NCI-2009-00643 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000390108
NCCTG-N0321
N0321 ( Other Identifier: North Central Cancer Treatment Group )
N0321 ( Other Identifier: CTEP )
U10CA025224 ( U.S. NIH Grant/Contract )
First Submitted: October 6, 2004
First Posted: October 8, 2004
Results First Submitted: November 25, 2013
Results First Posted: December 8, 2014
Last Update Posted: December 8, 2014
Last Verified: November 2013

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Bortezomib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action