Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	ECOG-E1303 SWOG-ECOG-E1303, E1303, NCT00077428

Objectives

Primary

1. 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

1. Determine the time to progression in patients treated with this drug.
2. Determine the overall survival of patients treated with this drug.
3. Determine the toxic effects of this drug in these patients.
4. 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.
5. Determine the toxic effects of this regimen in these patients.
6. Determine the profile and concentration of inflammatory and angiogenic cytokines in serum of patients before and in response to this regimen.
7. 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.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

Outcomes

Objective tumor response

Time to progression
Overall survival
Toxicity
Profile and concentration of inflammatory and angiogenic cytokines in serum
Correlation of the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway on tumor tissue with clinical activity

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.

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.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Athanassios Argiris, MD, Protocol chair		Ph: 412-648-6575
Barbara Burtness, MD, Protocol co-chair(Contact information may not be current)		Ph: 203-737-5064 Email: barbara.burtness@yale.edu

Southwest Oncology Group

Madeleine Kane, MD, PhD, Study coordinator		Ph: 720-848-0300; 800-473-2288 Email: madeleine.kane@uchsc.edu

Registry Information
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
Trial Start Date		2004-06-22
Trial Completion Date		2007-06-01
Registered in ClinicalTrials.gov		NCT00077428
Date Submitted to PDQ		2003-12-29
Information Last Verified		2007-08-23
NCI Grant/Contract Number		CA21115

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