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

This study has been completed.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00581360
First received: December 19, 2007
Last updated: January 9, 2014
Last verified: January 2014
  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.


Condition Intervention Phase
Adenoid Cystic Carcinoma
Drug: doxorubicin and bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Head and Neck Adenoid Cystic Carcinoma

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • To 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 ]

Secondary Outcome Measures:
  • To collect tumor tissue from previous diagnostic procedures and baseline blood specimens for future correlative studies [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: November 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
All subjects will receive doxorubicin and bortezomib
Drug: 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 Name: Velcade

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00581360

Locations
United States, Ohio
UPMC Cancer Center - Teramana Cancer Center - Steubenville
Steubenville, Ohio, United States, 43952
United States, Pennsylvania
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 -Haymaker Rd.
Monroeville, Pennsylvania, United States, 15146
UPMC Cancer Center -Mosside Blvd.
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
Sponsors and Collaborators
University of Pittsburgh
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Athanassios E Argiris, MD Principal Investigator
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00581360     History of Changes
Other Study ID Numbers: 06-124
Study First Received: December 19, 2007
Last Updated: January 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Adenoid cystic carcinoma
bortezomib
doxorubicin

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Adenoid Cystic
Adenocarcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Bortezomib
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014