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Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaPhase 1NCT00049283

Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

A Phase 1 study testing erlotinib hydrochloride, docetaxel and radiation therapy in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Stage III Squamous Cell Carcinoma of the Hypopharynx, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

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

Official record
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Trial summary

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
erlotinib hydrochloride, docetaxel and radiation therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Sep 2002to Feb 2008
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

  • Patients must have histologically or cytologically confirmed locally advanced (stage III or IV) squamous cell carcinoma of the head and neck without distant metastatic disease
  • No prior chemotherapy, radiation therapy, or investigational anti-tumor drug
  • Measurable disease within 4 weeks prior to registration according to the recommended RECIST response criteria
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Absolute neutrophil count >= 1,500/ul
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  • Platelets >= 100,000/ul
  • Hemoglobin >= 10 mg/dL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 5 x ULN when alkaline phosphatase is =< ULN
  • Alkaline phosphatase =< 5 x ULN when AST or ALT =< ULN
  • Prothrombin time within normal institutional limits
  • Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • No clinically significant heart disease (including NYHA class III or IV heart disease, significant arrhythmias requiring medication, symptomatic coronary artery disease, myocardial infarction within the previous six months, second or third degree heart block or bundle branch block)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter; women of childbearing potential must have a negative pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and willingness to sign a written informed consent document

Who cannot join

  • All histologies other than squamous cell carcinoma
  • Salivary gland and paranasal sinus squamous cell carcinoma
  • Patients who have had prior chemotherapy or radiotherapy
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases or direct cerebral invasion by tumor should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with intracranial extension (but without cerebral involvement) may still be eligible to participate
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 or docetaxel, including other drugs formulated with polysorbate 80
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  • No pre-existing peripheral neuropathy >= grade 2
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this protocol
  • HIV positive patients are excluded from participation
  • Patients with history of any other malignancy (except squamous cell or basal cell cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has elapsed since treatment of the previous cancer and the patient has remained continuously disease free
  • Patients who are felt to be poorly compliant

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Case Western Reserve University

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: A Phase I Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, OSI-774, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining erlotinib with docetaxel may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells. Phase I trial to study the maximum tolerated dose (MTD) of combining erlotinib with docetaxel and radiation therapy in treating patients who have locally advanced head and neck cancer

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine MTD and toxicity of combination of EGFR inhibitor (OSI-774), docetaxel, and radiation.

II. Pharmacokinetic profile of OSI-774 alone and in combination with docetaxel.

SECONDARY OBJECTIVES:

  1. Determine the overall and complete response rate of this combination.

II. Determine overall, disease free, and progression free survival of this combination.

  • EGFR expression and phosphorylation status
  • Serum markers of angiogenic activity VEGF, sVEGFR-2, sKIT, ICAM, PDGF
  • Fluorescence in situ hybridization (FISH) for EGFR, ERBB2, PDGFR-β for gene amplification
  • DNA-sequencing of EGFR and ERBB2 genes from DNA extracted from pretreatment biopsy material for mutation screening
  • Gene expression profiling on pre-treatment biopsy material to identify predictors of response to treatment
  • Apoptosis (TUNEL assay)
  • Ki67 (nuclear proliferation antigen).

OUTLINE: This is a dose-escalation study of erlotinib and docetaxel.

Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9. Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who had N2 or greater cervical lymph node involvement at baseline or have residual neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing is complete.

Cohorts of 3-6 patients receive escalating doses of erlotinib and docetaxel until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 16 weeks for 1 year after completion of erlotinib, every 24 weeks for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.

Being tested
erlotinib hydrochloride, docetaxel, radiation therapy, therapeutic conventional surgery, laboratory biomarker analysis
Medical subject headings
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.

  • erlotinib hydrochlorideDrug

    Also called CP-358,774, erlotinib, OSI-774

    Given orally

  • docetaxelDrug

    Also called RP 56976, Taxotere, TXT

    Given IV

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    Undergo radiotherapy

  • therapeutic conventional surgeryProcedure or surgery

    Undergo neck dissection

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00049283
Study groupRoleWhat they receive
Treatment (erlotinib hydrochloride, docetaxel, and radiation)ExperimentalPatients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9. Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who had N2 or greater cervical lymph node involvement at baseline or have residual neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing is complete.
Receives: Drug: erlotinib hydrochloride; Drug: docetaxel; Radiation: radiation therapy; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using Common Toxicity Criteria (CTC) version 3.0 (Phase I)

    Measured: 9 weeks

  2. Pharmacokinetic profile (Phase I)

    Measured: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 48, and 72 hours

  3. Time to disease progression (TTP) (Phase II)

    Measured: Up to 5.5 years

Secondary outcomes (5)

  1. Progression-free survival (PFS) (Phase II)

    Will be estimated by Kaplan-Meier method.

    Measured: From the date of treatment to date of death or date of disease progression, and to date of last follow-up for those still alive and progression free, assessed up to 5.5 years

  2. Overall survival (OS) (Phase II)

    Will be estimated by Kaplan-Meier method.

    Measured: From the date of treatment to date of death, and to date of last follow-up for those still alive, assessed up to 5.5 years

  3. True objective response rate (Phase II)

    Will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method.

    Measured: Up to 5.5 years

  4. Changes of EGFR expression and serum markers over time (Phase II)

    The Wilcoxon signed rank test (the non-parametric version of paired T-test) will be used.

    Measured: Baseline and up to 5.5 years

  5. Patterns of gene expression data (Phase II)

    Cluster analysis including hierarchical clustering, Gaussian clustering, k means clustering, will be used.

    Measured: Up to 5.5 years

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startSep 2002
  3. Primary completionFeb 2008
  4. Study completionFeb 2008

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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00049283
Sponsor's protocol ID
NCI-2012-03113
Other IDs
CWRU 1301, U01CA099168, U01CA062502
Status last verified
Jan 2013
First submitted
12 Nov 2002
Last updated
6 Jun 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing erlotinib hydrochloride, docetaxel and radiation therapy in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Stage III Squamous Cell Carcinoma of the Hypopharynx, run by National Cancer Institute (NCI) at 1 site 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 16 inclusion and 12 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 6 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using Common Toxicity Criteria (CTC) version 3.0 (Phase I) (time frame: 9 weeks). The study lists 3 primary outcomes in all. 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 NCT00049283.

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 6 Jun 2014.

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