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

January 23, 2013 updated by: National Cancer Institute (NCI)

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Eastern Cooperative Oncology Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Drug: bortezomib
Given IV
Other Names:
  • MLN341
  • LDP 341
  • VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Up to 10 years
Up to 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Time from randomization or registration to the earlier of disease recurrence or death from any cause, assessed up to 10 years
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.
Time from randomization or registration to date of death (from any cause) or date of last contact, assessed up to 10 years
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
Up to 1 hour post-treatment (course 2)
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.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Collaborators

Southwest Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2004

Primary Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

February 10, 2004

First Submitted That Met QC Criteria

February 11, 2004

First Posted (Estimate)

February 12, 2004

Study Record Updates

Last Update Posted (Estimate)

January 24, 2013

Last Update Submitted That Met QC Criteria

January 23, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02574
  • U10CA021115 (U.S. NIH Grant/Contract)
  • E1303
  • CDR0000350319 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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