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

NCT00581360 | Completed Phase 2 Results DMC

• 1 other identifier: 06-124
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 21

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.

Conditions

Adenoid Cystic Carcinoma

Keywords

Adenoid cystic carcinoma; bortezomib; doxorubicin

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  ORR is the number participants experiencing partial response (PR) + the number participants experiencing complete response (CR) / the number participants experiencing partial response (PR) + the number participants experiencing complete response (CR) + the number participants experiencing stable disease (SD) + the number participants experiencing progressive disease (PD). RECIST v1.0 criteria for Target Lesions was used: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest s

  Up to 5 years

• Stable Disease Rate

  Using RECIST v1.0 criteria, stable disease rate is the number participants experiencing stable disease (SD) / the number participants experiencing partial response (PR) + the number participants experiencing complete response (CR) + the number participants experiencing stable disease (SD) + the number participants experiencing progressive disease (PD).

  Up to 5 years

Secondary Outcomes (3)

• Number of Months of Progression-free Survival (PFS)

  Up to 5 years

• Number of Months of Survival

  Up to 5 years

• Median Duration of Stable Disease Response

  Up to 36 months

Study Arms (1)

Bortezomib + Doxorubicin

OTHER

Patients with incurable adenoid cystic carcinoma of the head and neck who receive doxorubicin and bortezomib

Drug: doxorubicin and bortezomib

Interventions

doxorubicin and bortezomib DRUG

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.

Also known as: Velcade

Bortezomib + Doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (21)

UPMC Cancer Center - Teramana Cancer Center - Steubenville

Steubenville, Ohio, 43952, United States

Location

UPMC Cancer Center - Beaver

Beaver, Pennsylvania, 15009, United States

Location

UPMC Cancer Center - Clairton

Clairton, Pennsylvania, 15025, United States

Location

UPMC Cancer Center - Arnold Palmer Pavilion - Greensburg

Greensburg, Pennsylvania, 15601, United States

Location

UPMC Cancer Center - Oakbrook Commons - Greensburg

Greensburg, Pennsylvania, 15601, United States

Location

UPMC Cancer Center - Indiana

Indiana, Pennsylvania, 15701, United States

Location

UPMC Cancer Center - John P. Murtha Pavilion - Johnstown

Johnstown, Pennsylvania, 15901, United States

Location

UPMC Cancer Center - McKeesport

McKeesport, Pennsylvania, 15132, United States

Location

UPMC Cancer Center -Haymaker Rd.

Monroeville, Pennsylvania, 15146, United States

Location

UPMC Cancer Center -Mosside Blvd.

Monroeville, Pennsylvania, 15146, United States

Location

UPMC Cancer Center - Sewickley Medical Oncology/Hematology Group

Moon Township, Pennsylvania, 15108, United States

Location

UPMC Cancer Center -Mt. Pleasant

Mount Pleasant, Pennsylvania, 15666, United States

Location

UPMC Cancer Center -New Castle

New Castle, Pennsylvania, 16105, United States

Location

UPMC Cancer Center -Delafield Rd.

Pittsburgh, Pennsylvania, 15215, United States

Location

UPMC Cancer Center - Mercy

Pittsburgh, Pennsylvania, 15219, United States

Location

University of Pittsburgh Cancer Institute-Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Cancer Center - Passavant

Pittsburgh, Pennsylvania, 15237, United States

Location

UPMC Cancer Center -Drake

Pittsburgh, Pennsylvania, 15241, United States

Location

UPMC Cancer Center - Uniontown

Uniontown, Pennsylvania, 15401, United States

Location

UPMC Cancer Center - Washington

Washington, Pennsylvania, 15301, United States

Location

UPMC Cancer Center -Wexford

Wexford, Pennsylvania, 15090, United States

Location

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Interventions

Doxorubicin; Bortezomib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rita Johnson, Associate Director of Clinical Research Services
• Organization: Clinical Research Services, UPCI

johnsonr1@upmc.edu

412-647-8571

Study Officials

• Athanassios E Argiris, MD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 27, 2007
• Study Start: November 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: November 7, 2016
• Results First Posted: November 7, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)