Adenoid Cystic CarcinomaPhase 2NCT00581360
Phase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Adenoid Cystic Carcinoma of the Head and Neck
A Phase 2 study testing doxorubicin and bortezomib in people with Adenoid Cystic Carcinoma, run by University of Pittsburgh at 21 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenoid Cystic Carcinoma
- What is being tested?
- doxorubicin and bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 21 sitesUnited States
- Study dates
- Nov 2007to Jun 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
UPMC Cancer Center - Beaver
Beaver, Pennsylvania, 15009
UPMC Cancer Center - Clairton
Clairton, Pennsylvania, 15025
UPMC Cancer Center - Arnold Palmer Pavilion - Greensburg
Greensburg, Pennsylvania, 15601
UPMC Cancer Center - Oakbrook Commons - Greensburg
Greensburg, Pennsylvania, 15601
UPMC Cancer Center - Indiana
Indiana, Pennsylvania, 15701
UPMC Cancer Center - John P. Murtha Pavilion - Johnstown
Johnstown, Pennsylvania, 15901
UPMC Cancer Center - McKeesport
McKeesport, Pennsylvania, 15132
UPMC Cancer Center -Haymaker Rd.
Monroeville, Pennsylvania, 15146
UPMC Cancer Center -Mosside Blvd.
Monroeville, Pennsylvania, 15146
UPMC Cancer Center - Sewickley Medical Oncology/Hematology Group
Moon Township, Pennsylvania, 15108
UPMC Cancer Center -Mt. Pleasant
Mount Pleasant, Pennsylvania, 15666
UPMC Cancer Center -New Castle
New Castle, Pennsylvania, 16105
UPMC Cancer Center -Delafield Rd.
Pittsburgh, Pennsylvania, 15215
UPMC Cancer Center - Mercy
Pittsburgh, Pennsylvania, 15219
University of Pittsburgh Cancer Institute-Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
UPMC Cancer Center - Passavant
Pittsburgh, Pennsylvania, 15237
UPMC Cancer Center -Drake
Pittsburgh, Pennsylvania, 15241
UPMC Cancer Center - Teramana Cancer Center - Steubenville
Steubenville, Ohio, 43952
UPMC Cancer Center - Uniontown
Uniontown, Pennsylvania, 15401
UPMC Cancer Center - Washington
Washington, Pennsylvania, 15301
UPMC Cancer Center -Wexford
Wexford, Pennsylvania, 15090
About this study
Official title: Phase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Head and Neck Adenoid Cystic Carcinoma
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.
Read the 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).
- Conditions
- Adenoid Cystic Carcinoma
- Being tested
- doxorubicin and bortezomib
- Keywords
- Adenoid cystic carcinoma, bortezomib, doxorubicin
- Medical subject headings
- Carcinoma, Adenoid Cystic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxorubicin and bortezomibDrug
Also called Velcade
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.
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib + Doxorubicin | Other | Patients with incurable adenoid cystic carcinoma of the head and neck who receive doxorubicin and bortezomib Receives: Drug: doxorubicin and bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: Up to 5 years
Secondary outcomes (3)
Number of Months of Progression-free Survival (PFS)
Number of months that participants experienced stable disease (the disease does not progress per RECIST v1.0 criteria - Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started)
Measured: Up to 5 years
Number of Months of Survival
Number of months that the participant was alive.
Measured: Up to 5 years
Median Duration of Stable Disease Response
Median number of months of Stable Disease Response Per RECIST v1.0 (Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started)
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2007 (estimated)
- Study startNov 2007
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenoid Cystic CarcinomaStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Athanassios E Argiris, MD, Principal investigator, Principal Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00581360
- Sponsor's protocol ID
- 06-124
- Status last verified
- Sep 2016
- First submitted
- 19 Dec 2007
- Last updated
- 7 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Head and Neck Adenoid Cystic Carcinoma
- ClinicalTrials.gov ID
- NCT00581360
- Acronym / sponsor ID
- 06-124
- Conditions
- Adenoid Cystic Carcinoma
- Keywords
- Adenoid cystic carcinoma, bortezomib, doxorubicin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Nov 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 27 Dec 2007 (estimated)
- Results
- Posted 7 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib + Doxorubicin | Other | Drug: doxorubicin and bortezomibPatients with incurable adenoid cystic carcinoma of the head and neck who receive doxorubicin and bortezomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxorubicin and bortezomibAlso: VelcadePatients 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. | Drug | Bortezomib + Doxorubicin |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 5 years
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
Stable Disease Rate
Time frame: Up to 5 years
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).
3 secondary outcomes
Number of Months of Progression-free Survival (PFS)
Time frame: Up to 5 years
Number of Months of Survival
Time frame: Up to 5 years
Median Duration of Stable Disease Response
Time frame: Up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Athanassios E Argiris, MD principal investigator
Principal Investigator
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing doxorubicin and bortezomib in people with Adenoid Cystic Carcinoma, run by University of Pittsburgh at 21 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2016.