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 - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI) Southwest Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00077428

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Head and Neck Cancer	Drug: bortezomib Drug: doxorubicin hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Head and Neck Cancer Salivary Gland Disorders Tonsils and Adenoids

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Myocet Bortezomib

U.S. FDA Resources

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

Primary Outcome Measures:

Objective tumor response [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to progression [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Profile and concentration of inflammatory and angiogenic cytokines in serum [ Designated as safety issue: No ]
Correlation of the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway on tumor tissue with clinical activity [ Designated as safety issue: No ]

Study Start Date:	June 2004
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Determine the time to progression in patients treated with this drug.
Determine the overall survival of patients treated with this drug.
Determine the toxic effects of this drug in these patients.
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.
Determine the toxic effects of this regimen in these patients.
Determine the profile and concentration of inflammatory and angiogenic cytokines in serum of patients before and in response to this regimen.
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

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

AST and ALT no greater than 2.5 times upper limit of normal
Bilirubin normal

Renal

Creatinine normal OR
Creatinine clearance at least 60 mL/min

Cardiovascular

LVEF at least lower limit of normal by MUGA
No history of congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Chemotherapy

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)

Endocrine therapy

Not specified

Radiotherapy

At least 3 weeks since prior radiotherapy

Surgery

At least 3 weeks since prior surgery

Other

More than 4 weeks since prior investigational drugs
No other concurrent anticancer therapy or agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00077428

Locations

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Lewistown Hospital
Lewistown, Pennsylvania, United States, 17044
Mount Nittany Medical Center
State College, Pennsylvania, United States, 16803
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, Wisconsin
Froedtert Hospital and Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Southwest Oncology Group

Investigators

Study Chair:	Athanassios Argiris, MD	UPMC Cancer Centers
Investigator:	Barbara A. Burtness, MD	Yale University
Investigator:	Madeleine A. Kane, MD, PhD	University of Colorado at Denver and Health Sciences Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Argiris A, Goldwasser MA, Burtness B, et al.: A phase II trial of PS-341 (bortezomib) followed by the addition of doxorubicin at progression in incurable adenoid cystic carcinoma of the head and neck: an Eastern Cooperative Oncology Group. [Abstract] J Clin Oncol 24 (Suppl 18): A-5573, 2006.

Study ID Numbers:	CDR0000350319, ECOG-E1303, SWOG-ECOG-E1303
Study First Received:	February 10, 2004
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00077428 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent adenoid cystic carcinoma of the oral cavity
stage III adenoid cystic carcinoma of the oral cavity
stage IV adenoid cystic carcinoma of the oral cavity
recurrent salivary gland cancer

stage III salivary gland cancer
stage IV salivary gland cancer
salivary gland adenoid cystic carcinoma

Study placed in the following topic categories:

Bortezomib
Disease Progression
Recurrence
Doxorubicin
Carcinoma
Protease Inhibitors
Anti-Bacterial Agents

Carcinoma, Adenoid Cystic
Head and Neck Neoplasms
Adenoid Cystic Carcinoma
Adenocarcinoma
Salivary Gland Diseases
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Bortezomib
Enzyme Inhibitors
Antibiotics, Antineoplastic
Pharmacologic Actions
Doxorubicin
Protease Inhibitors

Carcinoma
Neoplasms
Neoplasms by Site
Carcinoma, Adenoid Cystic
Head and Neck Neoplasms
Therapeutic Uses
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on August 30, 2009