Bortezomib and Gemcitabine in Treating Patients With Recurrent or Metastatic Nasopharyngeal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00305734
First received: March 21, 2006
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

This phase II trial is studying how well giving bortezomib together with gemcitabine works in treating patients with recurrent or metastatic nasopharyngeal cancer. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine may kill more tumor cells


Condition Intervention Phase
Recurrent Nasopharyngeal Cancer
Stage IV Nasopharyngeal Cancer
Drug: bortezomib
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of PS-341 (Bortezomib, NSC-681239) Followed by the Addition of Gemcitabine at Progression in Recurrent or Metastatic Nasopharyngeal Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective response rate (confirmed and unconfirmed, complete and partial response) based on the Response Evaluation Criteria in Solid Tumors (RECIST) in patients treated with bortezomib [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response probability (confirmed and unconfirmed, complete and partial response) based on the RECIST in patients treated with bortezomib and gemcitabine hydrochloride [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Progression-free survival rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    95% confidence intervals will be estimated.

  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Relationship between Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) level, NF-kB DNA- binding activity, and methylation status of E-cadherin promoter with clinical outcome [ Time Frame: Day 4 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: August 2006
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib, gemcitabine hydrochloride)

Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 2 additional courses of treatment with bortezomib.

Patients who experience disease progression on single-agent bortezomib and did not receive prior gemcitabine hydrochloride may begin combination therapy within 10-28 days of the last dose of bortezomib. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and bortezomib IV on days 1, 4, 8, 11. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 2 additional courses beyond the confirmed CR.

Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES: Primary I. Assess the response probability (confirmed and unconfirmed, complete and partial responses) and 3-month progression-free survival rate in patients with metastatic or recurrent nasopharyngeal carcinoma (NPC) who are treated with bortezomib.

Secondary I. Estimate 1-year progression-free survival and assess quantitative toxicities in this group of patients treated with bortezomib.

II. Evaluate the response probability (confirmed and unconfirmed, complete and partial) in the subset of patients who progress on bortezomib, with measurable disease at the time of progression, and go on to receive bortezomib and gemcitabine hydrochloride combination therapy.

III. Estimate 1-year overall survival of all patients treated with this regimen.

IV. Estimate 6-month progression-free survival from the start of combination therapy and assess quantitative toxicities in the subset of patients who progress on bortezomib and receive combination therapy.

V. Explore, in a preliminary manner, the relationship between changes in Epstein-Barr virus DNA level, NF-kB DNA-binding activity, and methylation status of E-cadherin promoter with clinical outcomes.

OUTLINE: This is a multicenter study of bortezomib.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses of treatment with bortezomib.

Patients who experience disease progression on single-agent bortezomib and did not receive prior gemcitabine hydrochloride may begin combination therapy within 10-28 days of the last dose of bortezomib. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and bortezomib IV on days 1, 4, 8, 11. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 2 additional courses beyond the confirmed CR.

After the completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed nasopharyngeal carcinoma (NPC) of one of the following subtypes:

    • Non-keratinizing (WHO type II)
    • Undifferentiated (WHO type III)
  • Disease meets one of the following stage criteria:

    • Stage IVC at diagnosis
    • Persisted, metastasized, or recurred after definitive surgery, radiotherapy, and/or chemotherapy
  • Measurable disease

    • If only measurable disease is within a prior radiation therapy port, disease progression must be clearly demonstrated
  • No known CNS metastases
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin normal
  • SGOT or SGPT ≤ 2.5 times ULN
  • Zubrod performance status 0-2
  • No peripheral neuropathy > grade 1
  • No prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for 5 years
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • More than 6 months since prior myocardial infarction
  • No New York Heart Association class III or IV cardiac problems
  • No uncontrolled angina
  • No severe uncontrolled ventricular arrhythmias
  • No acute ischemia by ECG
  • No active conduction system abnormalities
  • No known hypersensitivity to bortezomib, boron, or mannitol
  • See Disease Characteristics
  • No prior therapy with gemcitabine hydrochloride, bortezomib, or other proteasome inhibitors

    • No more than 28 days since discontinuation of single-agent bortezomib
    • Patients with prior gemcitabine hydrochloride treatment are eligible for single-agent bortezomib treatment but NOT for combination treatment
  • No more than one prior chemotherapy regimen for the treatment of metastatic or recurrent NPC

    • At least 28 days since prior treatment and recovered
  • At least 24 weeks since prior adjuvant chemotherapy
  • At least 24 weeks since prior chemotherapy as a radiosensitizer for initial locally advanced disease
  • At least 28 days since prior radiotherapy and recovered
  • At least 28 days since prior surgery and recovered
  • No other concurrent therapy for NPC, including any of the following:

    • Radiotherapy
    • Chemotherapy
    • Immunotherapy
    • Biologic therapy
    • Other investigational drugs
    • Gene therapy
  • No colony-stimulating factor therapy during the first course of study therapy
  • No concurrent highly active antiretroviral therapy (HAART) in HIV-positive patients
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305734

Locations
United States, Texas
Southwest Oncology Group
San Antonio, Texas, United States, 78245
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen Shibata Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00305734     History of Changes
Other Study ID Numbers: NCI-2012-02690, SWOG-S0506, U10CA032102, CDR0000462635
Study First Received: March 21, 2006
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nasopharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Gemcitabine
Bortezomib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014