Head and Neck CancerPhase 1/2NCT00077103
Induction Chemotherapy Using Doxorubicin and Cisplatin Followed by Combretastatin A4 Phosphate and Radiation Therapy in Treating Patients With Newly Diagnosed Regionally Advanced Anaplastic Thyroid Cancer
A Phase 1/2 study testing filgrastim, pegfilgrastim and cisplatin in people with Head and Neck Cancer, run by Case Comprehensive Cancer Center at 3 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combretastatin A4 phosphate may stop the growth of cancer by stopping blood flow to the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- filgrastim, pegfilgrastim and cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 4 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2003to Dec 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
DISEASE CHARACTERISTICS:
- Histologically confirmed anaplastic or poorly differentiated variant thyroid carcinoma of either of the following:
- Regionally advanced disease
- Confined to the neck and/or superior mediastinum (i.e., above the level of the carina)
- Measurable or evaluable* disease
- Completely resected disease without measurable or evaluable disease NOTE: *At a minimum, abnormalities on physical exam or radiographic studies that may not be precisely measured but readily followed
- Must have original/diagnostic tumor blocks available to confirm histopathology and for tumor microvessel density immunohistochemistry
- Patients with no available original/diagnostic tumor blocks must have tumor accessible for pretreatment needle core biopsy
- Must undergo indirect and direct laryngoscopy to ensure patency of the trachea/airway if deemed inoperable, with bulky thyroid/neck masses and/or suspicion of airway obstruction
- No distant metastases, including but not limited to, brain metastases, disease below the level of the carina, pulmonary parenchyma, and hepatic or bony metastases
- Superior mediastinal disease (i.e., above the level of the carina) in addition to regional neck disease is allowed provided the disease can be contained in a single radiotherapy port
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- At least 12 weeks
Hematopoietic
- Absolute granulocyte count ≥ 1,500/mm^3
- Platelet count ≥ 75,000/mm^3
- Hemoglobin ≥ 8.5 g/dL
Hepatic
- Bilirubin ≤ 1.5 mg/dL
- ALT and AST ≤ 3.5 times upper limit of normal
Renal
- Creatinine ≤ 1.5 mg/dL
Cardiovascular
- LVEF ≥ 50% by echocardiogram
- EKG normal
- No prior angina
- No prior myocardial infarction (e.g., significant Q waves), QTc > 450 msec, or other clinically significant abnormalities on ECG
- No congestive heart failure
- No uncontrolled atrial arrhythmias or clinically significant arrhythmias, including any of the following:
- Conduction abnormality
- Nodal junctional arrhythmias and dysrhythmias
- Sinus bradycardia or tachycardia
- Supraventricular arrhythmias
- Atrial fibrillation or flutter
- Syncope or vasovagal episodes
- No significant heart wall abnormality or heart muscle damage by echocardiogram
- No uncontrolled hypertension (i.e., blood pressure consistently greater than 150/100 mm Hg irrespective of medication)
- Hypertension is allowed provided there is clinical documentation of controlled blood pressure for 2 months before study entry
- No symptomatic peripheral vascular disease or cerebrovascular disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled hypokalemia or hypomagnesemia
- No concurrent serious infection
- No other nonmalignant uncontrolled medical illness or one whose control may be jeopardized by the complications of study therapy
- No grade 2 or greater pre-existing motor or sensory peripheral neuropathy
- No psychiatric disorder or other condition that would preclude study compliance
- No conditions associated with QTc prolongation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent biologic therapy
- No concurrent immunotherapy
Chemotherapy
- No prior chemotherapy
- No other concurrent chemotherapy
Endocrine therapy
- No concurrent hormonal therapy, except for the following:
- Gonadotropin-releasing hormone agonists for patients with hormone-refractory prostate cancer
- Hormone replacement therapy
- Oral contraceptives
- Megestrol for anorexia/cachexia
Radiotherapy
- No prior radiotherapy
- No concurrent radiotherapy
Surgery
- See Disease Characteristics
- Prior attempt at resection or cytoreduction (e.g., debulking) surgery irrespective of surgical margins allowed provided there are no distant metastases
- At least 1 week but no more than 8 weeks since prior surgery and recovered
Other
- No other concurrent cytotoxic therapy
- No other concurrent antineoplastic therapy
- No other concurrent investigational therapy
- No concurrent medications known to prolong the QTc interval unless the medication can be held for at least 4 days during each treatment course
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, 48202
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase II Trial of Combined Modality Combretastatin A-4 Phosphate (CA4P)-Based Therapy for Patients With Newly Diagnosed Anaplastic Thyroid Cancer [Induction Chemotherapy With Doxorubicin/Cisplatin; Combined Modality Therapy With CA4P and Radiation; Followed by 2 Cycles of CA4P Consolidation]
RATIONALE: Drugs used in chemotherapy, such as doxorubicin and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combretastatin A4 phosphate may stop the growth of cancer by stopping blood flow to the tumor. Combining doxorubicin and cisplatin with radiation therapy and combretastatin A4 phosphate may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving induction chemotherapy using doxorubicin and cisplatin together with radiation therapy and combretastatin A4 phosphate works in treating patients with newly diagnosed regionally advanced anaplastic thyroid cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the objective response rate in patients with newly diagnosed regionally advanced anaplastic thyroid cancer treated with induction chemotherapy comprising doxorubicin and cisplatin followed by combretastatin A4 phosphate (CA4P) and radiotherapy.
- Determine whether this regimen alters the natural history of anaplastic thyroid cancer by virtue of doubling the median survival of these patients from 10 to 20 months.
Secondary
- Determine a tolerable dose of CA4P when administered with radiotherapy in these patients. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Determine the safety profile of this regimen in these patients.
- Determine clinical predictors of response (e.g., pretreatment tumor microvessel density and immature vessel staining, changes in sICAM-1 levels and tumor blood flow, and pharmacokinetic parameters) in patients treated with this regimen.
- Correlate the diminution in blood flow with tumor pain and response in patients treated with this regimen.
OUTLINE: This is a multicenter study of combretastatin A4 phosphate (CA4P). (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Induction phase: Patients receive doxorubicin IV over 5-10 minutes and cisplatin IV over 30-60 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2.
- Combined modality phase: Beginning on day 22, patients undergo radiotherapy twice daily, 5 days a week, for 3-4 weeks. Patients also receive CA4P IV over 10 minutes weekly on the fifth day of radiotherapy.
Cohorts of 6 patients receive 1 of 2 escalating doses of CA4P to determine a tolerable dose. The tolerable dose is defined as the dose at which less than 2 of 6 patients experience dose-limiting toxicity. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Consolidation phase: Beginning 4-6 weeks after the completion of the combined modality phase, patients receive CA4P IV over 10 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses.
Treatment in all phases continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 2 months for 1 year and then every 3 months for 2 years from study entry.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study within 18 months.
- Conditions
- Head and Neck Cancer
- Being tested
- filgrastim, pegfilgrastim, cisplatin, doxorubicin hydrochloride, fosbretabulin disodium
- Keywords
- anaplastic thyroid cancer
- Medical subject headings
- Head and Neck Neoplasms, Thyroid Carcinoma, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2.
pegfilgrastimBiological
filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2.
cisplatinDrug
cisplatin IV over 30-60 minutes on day 1
doxorubicin IV over 5-10 minutes
fosbretabulin disodiumDrug
Also called Combretastatin A-4 Phosphate, CA4P
Combined Modality Phase:Patients also receive CA4P IV over 10 minutes weekly on the fifth day of radiotherapy. Beginning 4-6 weeks after the completion of the combined modality phase, patients receive CA4P IV over 10 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses.
radiation therapyRadiation
Beginning on day 22, patients undergo radiotherapy twice daily, 5 days a week, for 3-4 weeks.
What is being measured
The primary outcome is the main question the study is designed to answer.
Median survival
Measured: at months 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 33, and 36
Secondary outcomes (1)
Objective disease response
Measured: at the end of induction, combined modality therapy, and consolidation therapy, at 2 months after completion of consolidation therapy, at 2 month intervals during year 1, and then 3 month intervals during years 2 and 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2004 (estimated)
- Study startNov 2003
- Primary completionFeb 2007
- Study completionDec 2007
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Panayiotis Savvides, MD, Study chair, Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00077103
- Sponsor's protocol ID
- CWRU3302
- Other IDs
- P30CA043703, CASE-CWRU-3302, CWRU-040337, OXIGENE-CWRU-3302
- Status last verified
- Jun 2010
- First submitted
- 10 Feb 2004
- Last updated
- 11 Jun 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Combined Modality Combretastatin A-4 Phosphate (CA4P)-Based Therapy for Patients With Newly Diagnosed Anaplastic Thyroid Cancer [Induction Chemotherapy With Doxorubicin/Cisplatin; Combined Modality Therapy With CA4P and Radiation; Followed by 2 Cycles of CA4P Consolidation]
- ClinicalTrials.gov ID
- NCT00077103
- Acronym / sponsor ID
- CWRU3302
- Conditions
- Head and Neck Cancer
- Keywords
- anaplastic thyroid cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2003
- Primary completion
- Feb 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 11 Feb 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as doxorubicin and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combretastatin A4 phosphate may stop the growth of cancer by stopping blood flow to the tumor. Combining doxorubicin and cisplatin with radiation therapy and combretastatin A4 phosphate may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving induction chemotherapy using doxorubicin and cisplatin together with radiation therapy and combretastatin A4 phosphate works in treating patients with newly diagnosed regionally advanced anaplastic thyroid cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the objective response rate in patients with newly diagnosed regionally advanced anaplastic thyroid cancer treated with induction chemotherapy comprising doxorubicin and cisplatin followed by combretastatin A4 phosphate (CA4P) and radiotherapy.
- Determine whether this regimen alters the natural history of anaplastic thyroid cancer by virtue of doubling the median survival of these patients from 10 to 20 months.
Secondary
- Determine a tolerable dose of CA4P when administered with radiotherapy in these patients. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Determine the safety profile of this regimen in these patients.
- Determine clinical predictors of response (e.g., pretreatment tumor microvessel density and immature vessel staining, changes in sICAM-1 levels and tumor blood flow, and pharmacokinetic parameters) in patients treated with this regimen.
- Correlate the diminution in blood flow with tumor pain and response in patients treated with this regimen.
OUTLINE: This is a multicenter study of combretastatin A4 phosphate (CA4P). (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Induction phase: Patients receive doxorubicin IV over 5-10 minutes and cisplatin IV over 30-60 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2.
- Combined modality phase: Beginning on day 22, patients undergo radiotherapy twice daily, 5 days a week, for 3-4 weeks. Patients also receive CA4P IV over 10 minutes weekly on the fifth day of radiotherapy.
Cohorts of 6 patients receive 1 of 2 escalating doses of CA4P to determine a tolerable dose. The tolerable dose is defined as the dose at which less than 2 of 6 patients experience dose-limiting toxicity. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P)
- Consolidation phase: Beginning 4-6 weeks after the completion of the combined modality phase, patients receive CA4P IV over 10 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses.
Treatment in all phases continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 2 months for 1 year and then every 3 months for 2 years from study entry.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study within 18 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| filgrastimfilgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2. | Biological | – |
| pegfilgrastimfilgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2. | Biological | – |
| cisplatincisplatin IV over 30-60 minutes on day 1 | Drug | – |
| doxorubicin hydrochloridedoxorubicin IV over 5-10 minutes | Drug | – |
| fosbretabulin disodiumAlso: Combretastatin A-4 Phosphate, CA4PCombined Modality Phase:Patients also receive CA4P IV over 10 minutes weekly on the fifth day of radiotherapy. Beginning 4-6 weeks after the completion of the combined modality phase, patients receive CA4P IV over 10 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses. | Drug | – |
| radiation therapyBeginning on day 22, patients undergo radiotherapy twice daily, 5 days a week, for 3-4 weeks. | Radiation | – |
Primary outcome
Median survival
Time frame: at months 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 33, and 36
1 secondary outcome
Objective disease response
Time frame: at the end of induction, combined modality therapy, and consolidation therapy, at 2 months after completion of consolidation therapy, at 2 month intervals during year 1, and then 3 month intervals during years 2 and 3
Results and safety
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2010.
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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.
Panayiotis Savvides, MD study chair
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing filgrastim, pegfilgrastim and cisplatin in people with Head and Neck Cancer, run by Case Comprehensive Cancer Center at 3 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?
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: stopped early, as of the sponsor's last update on 11 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
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?
Median survival (time frame: at months 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 27, 30, 33, and 36). 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 11 Jun 2010; AzTrials last refreshed its copy on 7 Nov 2026.