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Trial record 15 of 73 for:    "Salivary Gland Neoplasms"

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

This study has been completed.
Sponsor:
Collaborator:
Southwest Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00077428
First received: February 10, 2004
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
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
Drug: bortezomib
Drug: doxorubicin 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 (NSC 681239) Followed by the Addition of Doxorubicin at Progression in Advanced Adenoid Cystic Carcinoma of the Head and Neck

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Estimated using Fisher's exact test at a two-sided 10% significance level.


Enrollment: 37
Study Start Date: June 2004
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

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

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
  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: NCT00077428

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Athanassios Argiris Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00077428     History of Changes
Other Study ID Numbers: NCI-2012-02574, E1303, U10CA021115, CDR0000350319
Study First Received: February 10, 2004
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Salivary Gland Neoplasms
Carcinoma
Carcinoma, Adenoid Cystic
Adenocarcinoma
Head and Neck Neoplasms
Mouth Diseases
Mouth Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Salivary Gland Diseases
Stomatognathic Diseases
Bortezomib
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014