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

Recurrent Salivary Gland Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00077428
• Other study ID #: NCI-2012-02574
• Secondary ID: E1303U10CA021115
• Status: Completed
• Phase: Phase 2
• First received: February 10, 2004
• Last updated: January 23, 2013
• Start date: June 2004

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Adenoid Cystic
• Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
• Recurrent Salivary Gland Cancer
• Salivary Gland Adenoid Cystic Carcinoma
• Salivary Gland Neoplasms
• 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

Intervention

Drug:
• bortezomib
Given IV
• doxorubicin hydrochloride
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Eastern Cooperative Oncology Group	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Southwest Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective tumor response (complete and partial overall response) as defined by Response Evaluation Criteria in Solid Tumors (RECIST)		Up to 10 years	No
Secondary	Toxicities, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0		Up to 30 days after last dose of study treatment	Yes
Secondary	Progression free survival	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	No
Secondary	Overall survival	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	No
Secondary	Association of change in cytokine concentration with response to bortezomib therapy	A Wilcoxon rank sum test at a two-sided 10% significance level will be used	Up to 1 hour post-treatment (course 2)	No
Secondary	Correlation of the expression of biomarkers which may be affected by the ubiquitin-proteasome degradation pathway on tumor tissue with clinical activity	Estimated using Fisher's exact test at a two-sided 10% significance level.	Baseline	No