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Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma (Cancer) of the Head and Neck

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ClinicalTrials.gov Identifier: NCT00077428
Recruitment Status : Completed
First Posted : February 12, 2004
Last Update Posted : January 24, 2013
Sponsor:
Collaborator:
Southwest Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE February 10, 2004
First Posted Date  ICMJE February 12, 2004
Last Update Posted Date January 24, 2013
Study Start Date  ICMJE June 2004
Actual Primary Completion Date June 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 10 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00077428 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
  • Toxicities, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Up to 30 days after last dose of study treatment ]
  • Progression free survival [ Time Frame: Time from randomization or registration to the earlier of disease recurrence or death from any cause, assessed up to 10 years ]
    Examined using Kaplan-Meier estimates.
  • Overall survival [ Time Frame: Time from randomization or registration to date of death (from any cause) or date of last contact, assessed up to 10 years ]
    Examined using Kaplan-Meier estimates.
  • Association of change in cytokine concentration with response to bortezomib therapy [ Time Frame: Up to 1 hour post-treatment (course 2) ]
    A Wilcoxon rank sum test at a two-sided 10% significance level will be used
  • Correlation of the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway on tumor tissue with clinical activity [ Time Frame: Baseline ]
    Estimated using Fisher's exact test at a two-sided 10% significance level.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bortezomib Followed by the Addition of Doxorubicin at Disease Progression in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma (Cancer) of the Head and Neck
Official Title  ICMJE Phase II Trial of PS-341 (NSC 681239) Followed by the Addition of Doxorubicin at Progression in Advanced Adenoid Cystic Carcinoma of the Head and Neck
Brief Summary This phase II trial is studying how well bortezomib followed by doxorubicin at the time of disease progression works in treating patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (cancer) of the head and neck. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with doxorubicin may kill more tumor cells
Detailed Description

OBJECTIVES: Primary I. Determine the objective tumor response in patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma of the head and neck treated with bortezomib.

Secondary I. Determine the time to progression in patients treated with this drug. II. Determine the overall survival of patients treated with this drug. III. Determine the toxic effects of this drug in these patients. IV. Determine the objective tumor response, time to progression, and overall survival of patients who progress on single-agent bortezomib and are then treated with doxorubicin and bortezomib.

V. Determine the toxic effects of this regimen in these patients. VI. Determine the profile and concentration of inflammatory and angiogenic cytokines in serum of patients before and in response to this regimen.

VII. Correlate the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway (NF-kB, p53, p27, cyclin D1, cyclin E, vascular endothelial growth factor [VEGF], MVD, V-CAM, and N-CAM) on tumor tissue with the clinical activity of bortezomib in these patients.

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression continue to receive bortezomib as above and doxorubicin IV over 2-5 minutes on days 1 and 8. Treatment repeats every 21 days for up to 14 courses in the absence of further disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 8 years.

PROJECTED ACCRUAL: A total of 23-37 patients will be accrued for this study within 2.3 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
  • Recurrent Salivary Gland Cancer
  • Salivary Gland Adenoid Cystic Carcinoma
  • Stage III Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage III Salivary Gland Cancer
  • Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage IV Salivary Gland Cancer
Intervention  ICMJE
  • Drug: bortezomib
    Given IV
    Other Names:
    • LDP 341
    • MLN341
    • VELCADE
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (bortezomib, doxorubicin hydrochloride)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression continue to receive bortezomib as above and doxorubicin IV over 2-5 minutes on days 1 and 8. Treatment repeats every 21 days for up to 14 courses in the absence of further disease progression or unacceptable toxicity.
Interventions:
  • Drug: bortezomib
  • Drug: doxorubicin hydrochloride
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 23, 2013)
37
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date June 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed adenoid cystic carcinoma of the head and neck

    • Locally advanced, recurrent, or metastatic disease that is considered incurable by known therapies
  • Unidimensionally measurable disease
  • Must not have stable disease for at least 9 months before study entry
  • No known brain metastases
  • Performance status - ECOG 0-2
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • AST and ALT no greater than 2.5 times upper limit of normal
  • Bilirubin normal
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • LVEF at least lower limit of normal by MUGA
  • No history of congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No active or ongoing infection
  • No prior allergy to compounds of similar chemical or biological composition to bortezomib
  • No other concurrent uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance
  • No pre-existing neuropathy > grade 1
  • No other invasive malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • See Chemotherapy
  • No prior anthracyclines, including any of the following:

    • Doxorubicin
    • Epirubicin
    • Daunorubicin
    • Idarubicin
  • No prior mitoxantrone
  • No prior high-dose chemotherapy for bone marrow transplantation
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • At least 3 weeks since prior radiotherapy
  • At least 3 weeks since prior surgery
  • More than 4 weeks since prior investigational drugs
  • No other concurrent anticancer therapy or agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00077428
Other Study ID Numbers  ICMJE NCI-2012-02574
E1303
U10CA021115 ( U.S. NIH Grant/Contract )
CDR0000350319 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Southwest Oncology Group
Investigators  ICMJE
Principal Investigator: Athanassios Argiris Eastern Cooperative Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date January 2013

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