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Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaPhase 1NCT00906360

Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

A Phase 1 study testing sunitinib malate, pharmacological study and 3-dimensional conformal radiation therapy in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Recurrent Metastatic Squamous Neck Cancer With Occult Primary, run by National Cancer Institute (NCI) at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of sunitinib when given together with cetuximab and radiation therapy in treating patients with locally advanced or recurrent squamous cell carcinoma of the head and neck. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sunitinib malate, pharmacological study and 3-dimensional conformal radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
12 sitesUnited States
Study dates
Jul 2008to Sep 2012
Phase
Phase 1
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

Who may be able to join

  • Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, meeting any of the following criteria:
  • Recurrent disease
  • Second primary locoregional recurrence* with no clinically measurable distant disease
  • Poor prognosis non-metastatic head and neck carcinoma (M0)
  • Must have undergone radiotherapy as a component of prior treatment
  • Not a candidate for surgical resection with curative intent
Show all 99Show fewer
  • Patients with high-risk features at resection or following resection for recurrence are eligible
  • Must have locoregional tumor amenable to radiotherapy or reirradiation with curative intent
  • Entire gross tumor recurrence volume must be able to be treated without exceeding a cumulative spinal cord dose of 50 Gy
  • Unresected tumors must be measurable according to RECIST
  • No known brain metastases
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/mm^³
  • ANC > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • INR and PTT ratio < 1.5
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine normal OR creatinine clearance > 60 mL/min
  • Urine protein no more than trace
  • Hematocrit ≥ 28%
  • Hemoglobin ≥ 9 g/dL
  • QTc < 500 msec
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • The following patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO and MUGA:
  • Asymptomatic on treatment
  • Prior anthracycline exposure
  • Prior central thoracic radiotherapy included the heart in the radiotherapy port
  • No clinical evidence of active infection of any type, including hepatitis B or C virus
  • Infections controlled with therapy are allowed
  • Patients with hepatitis B or C on antiviral therapy with no detectable virus are allowed
  • No immune deficiency and/or HIV positivity
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate
  • No gastrointestinal tract disease or condition, including any of the following, that impairs ability to retain sunitinib tablets:
  • Inability to take oral medication or a requirement for IV alimentation
  • Prior surgical procedures affecting absorption
  • Active peptic ulcer disease
  • None of the following conditions allowed:
  • Serious or nonhealing wound, ulcer, or bone fracture
  • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No significant concurrent medical or psychiatric illness which, in the opinion of the investigator, would interfere with the patient's ability to participate in the trial
  • No active carotid artery involvement
  • No history of documented thrombosis (pulmonary embolism within the past 12 months or deep vein thrombosis [DVT] within the past 6 months), known coagulopathies or thrombophilia, or evidence of DVT/thromboembolic event
  • No history of the following cardiovascular conditions :
  • Myocardial infarction within the past 12 months
  • Cardiac arrhythmia or serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia ≥ 3 beats in a row) within the past 12 months
  • Stable/unstable angina within the past 12 months
  • Symptomatic congestive heart failure within the past 12 months
  • Coronary/peripheral artery bypass graft or stenting within the past 12 months
  • No cerebral vascular disease, cerebrovascular accident (stroke), or transient ischemic attack within the past 6 months
  • QTc prolongation (QTc interval ≥ 500 msec)
  • New York Heart Association class III-IV congestive heart failure
  • Poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
  • Other significant ECG abnormalities
  • See Disease Characteristics
  • Recovered from all prior radiotherapy and chemotherapy
  • More than 4 months since prior radiotherapy to the head and neck
  • More than 2 weeks since prior hormone replacement therapy or hormonal contraceptives
  • More than 4 weeks since prior and no other concurrent investigational agents
  • At least 1 month since prior surgery (unless ambulatory within 48 hours)
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
  • Azole antifungals (ketoconazole, itraconazole)
  • Clarithromycin
  • Erythromycin
  • Diltiazem
  • Verapamil
  • HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir)
  • Delavirdine
  • At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:
  • Rifampin
  • Rifabutin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • St. John wort
  • Efavirenz
  • Tipranavir
  • Concurrent coumarin-derivative anticoagulants (e.g., warfarin up to 2 mg daily) allowed for prophylaxis of thrombosis
  • Concurrent use of medications known to affect the conductive system (e.g., beta-blockers, calcium channel blockers, or digoxin) allowed under investigator supervision
  • No concurrent agent with proarrhythmic potential, including any of the following:
  • Terfenadine
  • Quinidine
  • Procainamide
  • Disopyramide
  • Sotalol
  • Probucol
  • Bepridil
  • Haloperidol
  • Risperidone
  • Indapamide
  • Flecainide
  • No concurrent chronic steroid treatment for > 6 months (i.e., prednisolone doses > 10 mg/day or equivalent)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent amifostine
  • No concurrent commercial agent or therapy intended to treat head and neck cancer
  • No other concurrent anticancer therapy

Who cannot join

None listed.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Michigan University Hospital

    Ann Arbor, Michigan, 48109

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201-1595

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637-1470

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Evanston CCOP-NorthShore University HealthSystem

    Evanston, Illinois, 60201

  • Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

    Fort Wayne, Indiana, 46845

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Froedtert and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Central Illinois Hematology Oncology Center

    Springfield, Illinois, 60702

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

Other trials in United States

About this study

Official title: A Phase I Trial of Concurrent Chemoradiation/Chemoreirradiation With Cetuximab (ERBITUX®), Sunitinib, and Accelerated Radiation in Patients With Locally Advanced/High-risk/Recurrent Poor Prognosis Head and Neck Cancer

This phase I trial is studying the side effects and best dose of sunitinib when given together with cetuximab and radiation therapy in treating patients with locally advanced or recurrent squamous cell carcinoma of the head and neck. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving sunitinib together with cetuximab and radiation therapy may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety, the maximum tolerated dose, and the dose limiting toxicity of sunitinib malate when administered in combination with cetuximab and radiotherapy in patients with locally advanced, recurrent, or second primary poor prognosis, high-risk squamous cell carcinoma of the head and neck.

SECONDARY OBJECTIVES:

  1. To describe the toxicity profile of this regimen. II. To explore the tolerability and feasibility of sunitinib malate when administered in combination with cetuximab and radiotherapy in these patients.

III. To assess the best overall response rate (complete and partial response) after completion of treatment.

IV. To assess the locoregional control rate. V. To assess the distant control rate. VI. To assess the pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube.

OUTLINE: This is a dose-escalation study of sunitinib malate.

Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.

*NOTE: *Patients may have resection prior to enrollment on protocol provided they have high-risk features for recurrence.

Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic analysis of sunitinib malate and metabolites.

After completion of study treatment, patients are followed up periodically for up to 6 years.

Being tested
sunitinib malate, pharmacological study, 3-dimensional conformal radiation therapy, cetuximab
Medical subject headings
Salivary Gland Neoplasms, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sunitinib malateDrug

    Also called SU11248, sunitinib, Sutent

    Given orally or by percutaneous gastrostomy tube

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • 3-dimensional conformal radiation therapyRadiation

    Also called 3D conformal radiation therapy, 3D-CRT

    Undergo radiotherapy

  • cetuximabBiological

    Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225

    Given IV

Study groups in NCT00906360
Study groupRoleWhat they receive
Treatment (enzyme inhibitor and monoclonal antibody therapy)ExperimentalPatients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.
Receives: Drug: sunitinib malate; Other: pharmacological study; Radiation: 3-dimensional conformal radiation therapy; Biological: cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum-tolerated dose (MTD) of sunitinib malate

    MTD is defined as the dose level immediately below the non-tolerated dose. The study will utilize a standard "3+3" design to determine the MTD. Dose limiting toxicities (DLTs) used for determining escalation of dose will be those occurring within the period of radiotherapy. Toxicity will be summarized by type and severity using the National Cancer Institute (NCI) Common Terminology Criteria.

    Measured: Up to 7-9 weeks

Secondary outcomes (7)

  1. Objective tumor response rates

    Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The efficacy analysis population (an exploratory analysis of those patients on study for the MTD) will consist of all subjects who received at least 1 dose of sunitinib. Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

    Measured: From the start of the treatment to up to 6 years

  2. Locoregional control rates

    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

    Measured: Up to 6 years

  3. Disease control rates

    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

    Measured: Up to 6 years

  4. Locoregional recurrence rates

    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

    Measured: At 3 years

  5. Time to progression

    Time to progression using Kaplan-Meier product limit curves will be calculated.

    Measured: From the date of registration to the date of progressive disease or death from any cause

  6. Overall survival time

    Overall survival using Kaplan-Meier product limit curves will be calculated.

    Measured: From the date of registration to the date of death or date of last patient contact if censored

  7. Pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube

    Measured: Prior to and up to 24 hours after the start of sunitinib malate

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2009 (estimated)
  2. Study startJul 2008
  3. Primary completionSep 2012

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00906360
Sponsor's protocol ID
NCI-2009-00279
Other IDs
UCIRB 16051B, CDR0000601544, UCIRB-16051B, N01CM62201
Status last verified
Jul 2013
First submitted
20 May 2009
Last updated
2 Jul 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sunitinib malate, pharmacological study and 3-dimensional conformal radiation therapy in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Recurrent Metastatic Squamous Neck Cancer With Occult Primary, run by National Cancer Institute (NCI) at 12 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 99 inclusion and 0 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: stopped early, as of the sponsor's last update on 2 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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 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.

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. 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?

Maximum-tolerated dose (MTD) of sunitinib malate (time frame: Up to 7-9 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00906360.

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 2 Jul 2013.

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