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Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaPhase 2NCT00939627

Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab

A Phase 2 study testing cetuximab, sorafenib tosylate and laboratory biomarker analysis 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 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cetuximab, sorafenib tosylate and laboratory biomarker analysis
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
55 participants
Where
8 sitesUnited States
Study dates
Jul 2009to Jan 2014
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 with recurrent, refractory or metastatic squamous cell carcinoma of oral cavity, oropharynx and larynx, hypopharynx or paranasal sinus, head and neck unknown primary or nasopharyngeal carcinoma WHO type 1; patients with recurrent, refractory or metastatic squamous cell carcinoma of oral cavity, oropharynx and larynx, hypopharynx or paranasal sinus, head and neck unknown primary or nasopharyngeal carcinoma WHO type 1; patients may have had up to 1 prior palliative chemotherapy for recurrent or metastatic disease; please note that chemotherapy given as part of a regimen for curative intent for recurrent disease does not count as "prior chemotherapy;" patients must not presently be candidates for curative therapy
  • ECOG performance status 0, 1 or 2
  • Hemoglobin >= 9.0/dl
  • Absolute-neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.5 x ULN
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  • ALT and AST =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement)
  • INR < 1.5 or a PT and PTT within normal limits
  • Creatinine =< 1.5 x ULN
  • If primary therapy was given for curative intent, at least 4 weeks must have elapsed after completion of primary therapy prior to enrollment on this clinical trial; however, toxicities from prior treatment must have resolved to grade 1 or less
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of the treatment; women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation (i.e, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for a minimum of 3 months following the last dose of chemotherapy; male subject agrees to use an acceptable method for contraception for the duration of the study and for a minimum of 3 months following the last dose of chemotherapy
  • Patients must have a measurable disease defined by RECIST criteria
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care; patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial

Who cannot join

  • Prior treatment with sorafenib or cetuximab
  • Patients with active clinically significant infection or with a fever >= 38.5º C within 3 days of the first scheduled day of protocol treatment
  • History of prior malignancy within the past 3 years except for curatively treated basal cell carcinoma and squamous cell carcinoma of the skin, CIN or localized prostate cancer with a current PSA < 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of study entry
  • Patients with known hypersensitivity to sorafenib or cetuximab
  • Prior severe infusion reaction to a monoclonal antibody
  • History of hand-foot syndrome
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  • Pregnant or lactating; sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized
  • Known untreated brain metastasis; patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis or progression of brain metastasis; patients with treated brain metastasis are eligible for study as long as no evidence of progression of CNS disease; hemorrhagic brain metastases are not allowed on study
  • Uncontrolled comorbid illness
  • Patients with HIV who are taking antiretroviral mediations will be excluded because of the potential interactions of anti-retroviral medications with these agent; however, given the potential immune modulating effects of sorafenib, investigators should still be very cautious about placing HIV positive patients on this trial as the effects of these medications on the HIV virus itself are not know
  • History of allogeneic transplant
  • Patient has received other investigational drugs within 28 days before enrollment
  • Cardiac disease: congestive heart failure > class II NYHA; patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension (defined as defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction will also be excluded from study; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy will also be excluded from study
  • Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Pulmonary hemorrhage/bleeding event > CTCAE grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of first dose of study drug
  • Tumor that invades the carotid artery as shown unequivocally by imaging studies
  • Serious non-healing wound, ulcer, or bone fracture
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug
  • Use of St. John's Wort or rifampin (rifampicin)
  • Use of the following medications will not be allowed within 4 weeks prior to enrollment on the study and during the study: ketoconazole, itraconazole, ritonavir, cyclosporine, carbamazepine, phenytoin, phenobarbital; products containing grapefruit juice will not be allowed while on study
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial
  • Any malabsorption problem
  • Known HIV positive patients will be excluded from trial due to the potential immune modulation that these agents may cause

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Suburban Hospital

    Bethesda, Maryland, 20814

  • Billings Clinic

    Billings, Montana, 59107-7000

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Montefiore Medical Center

    The Bronx, New York, 10467-2490

Other trials in United States

About this study

Official title: Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab in Patients With Refractory, Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

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. Sorafenib tosylate 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. It is not yet known whether cetuximab is more effective when given alone or together with sorafenib tosylate in treating patients with head and neck cancer. This randomized phase II trial is studying cetuximab to see how well it works when given together with or without sorafenib tosylate in treating patients with refractory, recurrent, and/or metastatic head and neck cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Compare the progression free survival (PFS) of the combination of cetuximab and sorafenib to that of cetuximab alone in patients with recurrent, refractory or metastatic squamous cell carcinoma of the head and neck (SCCHN).

SECONDARY OBJECTIVES:

  1. To evaluate the response rate, overall survival (OS) and toxicity of the combination of cetuximab and sorafenib and of cetuximab alone.

II. To evaluate the presence of EGFRvIII mutation, increased EGFR gene copy number and activated EGFR gene expression signature, and correlate with clinical parameters (RR, OS and PFS) in the cetuximab alone and cetuximab/sorafenib arms.

III. To evaluate whether VEGF receptor family and their ligand expression can predict response to cetuximab/sorafenib.

IV. To determine the proteomic profiles in serum and tumors that can predict the response and survival upon the treatment with cetuximab or cetuximab/sorafenib.

  1. To evaluate the effect of therapy on both general and head and neck specific functionality, symptom burden and QOL.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. (oral placebo closed as of 02/18/2010).

ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate twice daily on days 1-21.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Paraffin embedded tissue samples are collected at baseline for pharmacogenomic studies and blood samples are collected at baseline and for the first 3 courses for research purposes. Quality of life and symptom burden are assessed by Vanderbilt Head and Neck Symptom Survey, FACT-HN, and Fatigue and Pain Inventory questionnaires at baseline, at day 43, and at 3 and 6 months.

After completion of study treatment, patients are followed periodically for 3 years.

Being tested
cetuximab, placebo, sorafenib tosylate, laboratory biomarker analysis, quality-of-life assessment
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.

  • cetuximabBiological

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

    Given IV

  • placeboOther

    Also called PLCB

    Given orally

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given orally

  • laboratory biomarker analysisOther

    Correlative studies

  • quality-of-life assessmentProcedure or surgery

    Also called quality of life assessment

    Ancillary studies

Study groups in NCT00939627
Study groupRoleWhat they receive
Arm I (cetuximab and placebo)Placebo comparatorPatients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21.
Receives: Biological: cetuximab; Other: placebo; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment
Arm II (cetuximab and sorafenib tosylate)ExperimentalPatients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate twice daily on days 1-21.
Receives: Biological: cetuximab; Drug: sorafenib tosylate; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

What is being measured

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

  1. Progression Free Survival (PFS)

    Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as >=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.

    Measured: On-study date to lesser of date of progression or date of death from any cause (assessed up to 3 years)

Secondary outcomes (5)

  1. Best Response

    Number of patients in each response category, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of longest diameter (LD) of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD.

    Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD.

    Measured: On-treatment date to date of disease progression (assessed up to 3 years)

  2. Overall Survival (OS)

    Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details)

    Measured: On-study date to date of death from any cause (assessed up to 3 years)

  3. Number of Participants With Each Worst-Grade Toxicity

    Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death

    Measured: On-study date to 30 days following final dose of study drug

  4. Gene Expression Levels

    Formalin-fixed, paraffin-embedded (FFPE) tumors were collected. The FFPE tumors were to be evaluated for p16 expression using immunohistochemistry staining with antibody. Gene Expression Levels (positive when >70% cells stained, otherwise negative) were to be described using frequencies.

    Measured: Pre-therapy

  5. Overall Survival Associated With Immunomodulatory Cytokines

    Twelve immunomodulatory cytokines were selected based on previous a feasibility study and detected using multiplex Luminex bead assays from patient's plasma. One cytokines, HGF, was eliminated due to extremely low expression. Three representative cytokines, TGF-beta 1, IL-8 and VEGF were to be evaluated for association with survival due to clustering.

    Measured: Pre-therapy, up to about 42 months (follow-up for overall survival)

Timeline

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

  1. First posted15 Jul 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionJan 2013
  4. Study completionJan 2014

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00939627
Sponsor's protocol ID
NCI-2012-02847
Other IDs
NCI-2012-02847, MCC-15780, 8070, P30CA076292, N01CM00100
Status last verified
Dec 2017
First submitted
14 Jul 2009
Last updated
10 Mar 2026

Publications

  • Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.

    PubMed 25057165

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cetuximab, sorafenib tosylate and laboratory biomarker analysis 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 8 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 13 inclusion and 25 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 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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. Some participants in this study may receive a placebo. 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 1 Sep 2015). 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?

Progression Free Survival (PFS) (time frame: On-study date to lesser of date of progression or date of death from any cause (assessed up to 3 years)). 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 NCT00939627, which also lists 1 linked publication.

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 10 Mar 2026.

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