Phase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Adenoid Cystic Carcinoma of the Head and Neck

Overview[ - collapse ][ - ]

Purpose This is a Phase II trial non-randomized study to evaluate the objective response rate and stable disease rate (primary endpoints), progression-free survival, overall survival and toxicities with the combination of doxorubicin and bortezomib in patients with incurable head and neck adenoid cystic carcinoma. Also, we plan to collect tumor tissue from previous diagnostic procedures and baseline blood specimens for future correlative studies.
ConditionAdenoid Cystic Carcinoma
InterventionDrug: doxorubicin and bortezomib
PhasePhase 2
SponsorUniversity of Pittsburgh
Responsible PartyUniversity of Pittsburgh
ClinicalTrials.gov IdentifierNCT00581360
First ReceivedDecember 19, 2007
Last UpdatedJanuary 9, 2014
Last verifiedJanuary 2014

Tracking Information[ + expand ][ + ]

First Received DateDecember 19, 2007
Last Updated DateJanuary 9, 2014
Start DateNovember 2007
Estimated Primary Completion DateJune 2011
Current Primary Outcome MeasuresTo evaluate the objective response rate and stable disease rates, progression-free survival, overall survival and toxicities with the combination of doxorubicin and bortezomib in patients with incurable head and neck adenoid cystic carcinoma. [Time Frame: 5 years] [Designated as safety issue: Yes]
Current Secondary Outcome MeasuresTo collect tumor tissue from previous diagnostic procedures and baseline blood specimens for future correlative studies [Time Frame: 5 years] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitlePhase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Adenoid Cystic Carcinoma of the Head and Neck
Official TitlePhase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Head and Neck Adenoid Cystic Carcinoma
Brief Summary
This is a Phase II trial non-randomized study to evaluate the objective response rate and
stable disease rate (primary endpoints), progression-free survival, overall survival and
toxicities with the combination of doxorubicin and bortezomib in patients with incurable
head and neck adenoid cystic carcinoma. Also, we plan to collect tumor tissue from previous
diagnostic procedures and baseline blood specimens for future correlative studies.
Detailed Description
Patients will be treated with bortezomib 1.3 mg/m2, intravenously on days 1, 4, 8 and 11,
and doxorubicin 20 mg/m2, intravenously on days 1 and 8, every 21 days. Zinecard will be
added at the 8th cycle and all subsequent cycles with doxorubicin. After the completion of
14 cycles, if there is no progression, bortezomib once a week at a dose of 1.6 mg/m2 on days
1,8,15, every 28 days, will be administered alone. Treatment will continue unless disease
progression or intolerable toxicity emerges (see section 5 for detailed treatment plan and
dose modifications).
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionAdenoid Cystic Carcinoma
InterventionDrug: doxorubicin and bortezomib
Patients will be treated with bortezomib 1.3 mg/m2, intravenously on days 1, 4, 8 and 11, and doxorubicin 20 mg/m2, intravenously on days 1 and 8, every 21 days. Zinecard will be added at the 8th cycle and all subsequent cycles with doxorubicin. After the completion of 14 cycles, if there is no progression, bortezomib once a week at a dose of 1.6 mg/m2 on days 1,8,15, every 28 days, will be administered alone. Treatment will continue unless disease progression or intolerable toxicity emerges.
Other Names:
Velcade
Study Arm (s)Other: 1
All subjects will receive doxorubicin and bortezomib

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment10
Estimated Completion DateJune 2011
Estimated Primary Completion DateJune 2011
Eligibility Criteria
Inclusion Criteria:

- Patients must have locally advanced, recurrent, or metastatic adenoid cystic
carcinoma of the head and neck which is considered incurable by known therapies, as
judged by the investigator.

- Patients should have cytologically or histologically confirmed adenoid cystic
carcinoma of the head and neck.

- Patients must have unidimensionally measurable disease (RECIST criteria). If the only
site of measurable disease is a previously irradiated area, the patient must have
documented progression of disease in this area.

- All available prior computed tomography (CT) or magnetic resonance imaging (MRI)
scans should be reviewed and noted, and measurements showing progression of disease
should be documented whenever possible. However, documentation of disease progression
is not mandatory for enrollment.

- Patients must have multigated acquisition scan (MUGA) scan showing left ventricular
ejection function (LVEF) at or above the institutional lower limits of normal.

- Patients must have ECOG performance status 0-2.

- Patients should have recovered from prior surgery or radiation therapy. A minimum
time period of 3 weeks should elapse between the completion of extensive radiation
therapy for recurrent/metastatic disease and enrollment in the study.

- Patients must have normal organ and marrow function (as defined below) measured
within one week prior to registration:

- Absolute neutrophil count >1,500/mm3.

- Platelets greater than or equal to 100,000/mm3.

- Total bilirubin within normal institutional limits.

- Transaminases (AST and ALT) <3 X ULN.

- Creatinine within normal institutional limits or creatinine clearance (CrCl) greater
than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal. CrCl will be calculated using the Cockcroft-Gault formula:

- Calculated Creatinine Clearance = (140-age) X actual body wt.(kg) 72 X serum
creatinine. Multiply this number by 0.85 if the patient is female.

- Myocardial infarction within 6 months prior to enrollment, uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
acute ischemia or active conduction system abnormalities. Prior to study entry, any
ECG abnormality at screening has to be documented by the investigator as not
medically relevant. Patients must not have history of congestive heart failure of any
grade according to Heart Association (NYHA) (see Appendix 2).

- Age > 18 years and capacity to give informed consent.

- All patients must have given signed, informed consent prior to registration to the
study.

Exclusion Criteria:

- No prior chemotherapy for recurrent / metastatic adenoid cystic carcinoma. Up to 1
prior biologic/targeted therapy regimen is allowed. Also, chemotherapy as part of
initial potentially curative therapy (i.e. concurrent chemoradiotherapy) is allowed,
if it was completed >6 months earlier.

- Patients must not have any prior anthracyclines (doxorubicin, epirubicin,
daunorubicin, idarubicin) or mitoxantrone, or bortezomib.

- No history of prior malignancy, with the exception of curatively treated squamous
cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a
3-year disease-free interval.

- Patients must not have history of allergic reactions attributed to compounds of
similar chemical or biologic composition to bortezomib, boron or mannitol.

- Patients must not have any pre-existing neuropathy of grade > 1.

- Patients must not have uncontrolled intercurrent illness including, but not limited
to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements.

- Female patients who are pregnant or breast feeding or patients of reproductive
potential not using an effective method of birth control will be excluded. Women of
childbearing potential must have a negative serum pregnancy test within 2 weeks of
the first administration of chemo. Also, male patients whose sexual partners are
women of child bearing potential not using effective birth control will be excluded.

- Patients with known positivity for human immunodeficiency virus (HIV) will be
excluded due to possible pharmacokinetic interactions with bortezomib. Appropriate
studies will be undertaken in HIV-positive patients who are receiving or not
receiving combination anti-retroviral therapy when indicated.

- Patient must not have received other investigational drugs within 14 days before
enrollment.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00581360
Other Study ID Numbers06-124
Has Data Monitoring CommitteeYes
Information Provided ByUniversity of Pittsburgh
Study SponsorUniversity of Pittsburgh
CollaboratorsMillennium Pharmaceuticals, Inc.
Investigators Principal Investigator: Athanassios E Argiris, MD Principal Investigator
Verification DateJanuary 2014

Locations[ + expand ][ + ]

UPMC Cancer Center - Teramana Cancer Center - Steubenville
Steubenville, Ohio, United States, 43952
UPMC Cancer Center - Beaver
Beaver, Pennsylvania, United States, 15009
UPMC Cancer Center - Clairton
Clairton, Pennsylvania, United States, 15025
UPMC Cancer Center - Oakbrook Commons - Greensburg
Greensburg, Pennsylvania, United States, 15601
UPMC Cancer Center - Arnold Palmer Pavilion - Greensburg
Greensburg, Pennsylvania, United States, 15601
UPMC Cancer Center - Indiana
Indiana, Pennsylvania, United States, 15701
UPMC Cancer Center - John P. Murtha Pavilion - Johnstown
Johnstown, Pennsylvania, United States, 15901
UPMC Cancer Center - McKeesport
McKeesport, Pennsylvania, United States, 15132
UPMC Cancer Center -Mosside Blvd.
Monroeville, Pennsylvania, United States, 15146
UPMC Cancer Center -Haymaker Rd.
Monroeville, Pennsylvania, United States, 15146
UPMC Cancer Center - Sewickley Medical Oncology/Hematology Group
Moon Township, Pennsylvania, United States, 15108
UPMC Cancer Center -Mt. Pleasant
Mt. Pleasant, Pennsylvania, United States, 15666
UPMC Cancer Center -New Castle
New Castle, Pennsylvania, United States, 16105
University of Pittsburgh Cancer Institute-Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
UPMC Cancer Center -Delafield Rd.
Pittsburgh, Pennsylvania, United States, 15215
UPMC Cancer Center -Drake
Pittsburgh, Pennsylvania, United States, 15241
UPMC Cancer Center - Mercy
Pittsburgh, Pennsylvania, United States, 15219
UPMC Cancer Center - Passavant
Pittsburgh, Pennsylvania, United States, 15237
UPMC Cancer Center - Uniontown
Uniontown, Pennsylvania, United States, 15401
UPMC Cancer Center - Washington
Washington, Pennsylvania, United States, 15301
UPMC Cancer Center -Wexford
Wexford, Pennsylvania, United States, 15090