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

NCT ID: NCT00077428

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

bortezomib

Given IV

Intervention Type: DRUG

doxorubicin hydrochloride

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

LDP 341; MLN341; VELCADE; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Athanassios Argiris

Role: PRINCIPAL_INVESTIGATOR

Eastern Cooperative Oncology Group

Locations

Eastern Cooperative Oncology Group

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

E1303

Identifier Type: -

Identifier Source: secondary_id

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000350319

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02574

Identifier Type: -

Identifier Source: org_study_id