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Recurrent Head and Neck CancerPhase 3NCT00088907

Phase III Trial Of Docetaxel Versus Docetaxel Plus ZD1839 In Head And Neck Cancer

A Phase 3 study testing docetaxel and gefitinib in people with Recurrent Head and Neck Cancer and Metastatic Head and Neck Cancer, run by National Cancer Institute (NCI) at 1 site 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

Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining docetaxel with gefitinib may kill more tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
docetaxel and gefitinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
270 participants
Where
1 siteUnited States
Study dates
Aug 2004to Aug 2012
Phase
Phase 3
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

  • Histologically or cytologically confirmed squamous cell carcinoma of the head and neck; patient must not have nasopharyngeal carcinoma of histologic types World Health Organization (WHO) 2 and 3
  • Metastatic or locally recurrent carcinoma of the head and neck that is considered incurable by local therapies
  • Any number of prior chemotherapy or biologic/targeted therapy regimens is allowed
  • No prior systemic EGFR inhibitors, such as ZD1839 (Iressa, gefitinib)/Iressa (AstraZeneca), ABX-EBX (Abgenix), MDX-447 (Medarex/Merck), OSI-774/Tarceva (OSI pharmaceuticals), C225/Cetuximab (ImClone), PKI166 (Novartis), CI-1033 (Parke-Davis), EKB-569 (Wyeth Ayerst); treatment with paclitaxel is allowed if the patient did not progress while on paclitaxel
  • NOTE: the use of cetuximab given concurrently with radiation or chemoradiotherapy for up to 9 total weekly doses, as part of initial potentially curative therapy is allowed, if completed > 6 months prior to registration
  • Patients must not receiving any other investigational agent while on the study
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  • Patients must have either:
  • Strata A:
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 (in bed 50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities; up and about more than 50% of waking hours), AND no prior chemotherapy for recurrent metastatic head and neck cancer OR
  • Strata B
  • PS 0-2 AND prior chemotherapy (i.e. one or more prior chemotherapy regimens (without docetaxel)) for locally recurrent/metastatic disease or exposure to prior chemotherapy (without docetaxel) as part of primary curative therapy < 6 months prior to randomization; patients who receive chemotherapy as part of potentially curative therapy of primary disease within 6 months of randomization will be considered as having prior chemotherapy for recurrent/metastatic disease, whereas patients who received chemotherapy as part of potentially curative therapy of disease > 6 months of randomization will be considered as having no prior chemotherapy for recurrent/metastatic disease
  • Patients must have fully recovered from the effects of any prior surgery, chemotherapy, or radiation therapy
  • A minimum time period of 3 weeks must elapse between the completion of radiation therapy and randomization to the study
  • A minimum period of 4 weeks must elapse between the last administration of any prior chemotherapy and randomization to the study
  • At least 2 weeks must elapse between the last administration of biologic/targeted therapy and randomization to the study
  • Patients must be > 3 weeks since major surgery, or significant traumatic injury prior to randomization
  • Absolute neutrophil count (ANC) >= 1500 /mm^3
  • Platelets >= 100,000 /mm^3
  • Hemoglobin >= 8.0 g/dl
  • Bilirubin within normal limits
  • Creatinine < 2.0 or creatinine clearance of > 60 ml/min
  • All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception while on treatment and for three months after the completion of treatment
  • Patients must have measurable or non-measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST); baseline measurements and evaluations must be obtained < 4 weeks of randomization; all areas of disease should be recorded and mapped out in order to assess response and uniformity of response to therapy; disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy; persistent disease after radiotherapy must be biopsy proven at least 8 weeks after completion of radiation therapy
  • Radiographic findings are acceptable providing that clear-cut measurements can be made
  • Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 5 years post diagnosis
  • Drugs that are Cytochrome P450 3A4 (CYP3A4) inhibitors should be generally avoided and if possible, discontinued, 1 week prior to initiating study drug; however, if medically necessary, they can be taken with caution after consulting with the study chair
  • From patients consenting to participate in the correlative studies:
  • Tissues must be submitted as outlined in Section 10; if tissue cannot be submitted, written justification must be submitted to the ECOG Pathology Coordinating Office

Who cannot join

  • Prior therapy with docetaxel at any time (even if part of prior curative treatment)
  • Unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or serious arrhythmia requiring medication
  • Hypercalcemia related to head and neck cancer
  • Brain metastasis
  • Current peripheral neuropathy >= grade 2 at time of randomization
  • Patients have co-existing condition that would preclude full compliance with the study
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  • Known hypersensitivity to ZD1839 (Iressa, gefitinib) or any excipients of this product; prior history of severe hypersensitivity reaction to Docetaxel or other drugs formulated with polysorbate 80
  • HIV positive patient's receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with ZD1839 (Iressa, gefitinib)
  • Patients have had tumor-related hemorrhagic events in the previous three months that required as major medical intervention, such as surgery or embolization
  • Patients are on therapeutic anticoagulation or have tumors that are unequivocally invading major vessels (e.g. carotid artery)
  • Females are pregnant or breast feeding because chemotherapy may be harmful to the fetus or the nursing infant; also, the effects of ZD1839 (Iressa, gefitinib) on the developing human fetus are unknown

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase III Randomized, Placebo Controlled, Trial of Docetaxel Versus Docetaxel Plus ZD1839 (Iressa, Gefitinib) in Performance Status 2 or Previously Treated Patients With Recurrent or Metastatic Head and Neck Cancer

Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining docetaxel with gefitinib may kill more tumor cells. It is not yet known whether docetaxel is more effective with or without gefitinib in treating head and neck cancer. This randomized phase III trial is studying docetaxel and gefitinib to see how well they work compared to docetaxel alone in treating patients with metastatic or locally recurrent head and neck cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the survival of poor prognosis patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with docetaxel with or without ZD1839 (Iressa, gefitinib).

SECONDARY OBJECTIVES:

  1. To determine the time to progression and response rate in poor prognosis patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with docetaxel with or without ZD1839 (Iressa, gefitinib).

II. To correlate the expression and activation status of the epidermal growth factor receptor (EGFR) signaling pathway with clinical outcome in the above patient population. The following specific biomarkers will be measured by immunohistochemistry on paraffin-embedded tumor tissue: EGFR, p-EGFR, AKT, p-AKT, Transforming growth factor (TGF)-alpha, Ki-67, extracellular-signal-regulated kinase (ERK), p-ERK, p70s6, p- p70s6 , and p27.

III. To evaluate the frequency of common polymorphisms of Cytochrome P450 3A (CYP3A) and EGFR in this study population and the impact of these polymorphisms on survival, time to progression, response rate, and toxicities.

IV. To analyze docetaxel and ZD1839 (Iressa, gefitinib) pharmacokinetics and to correlate polymorphisms with pharmacokinetic variability, response, toxicity, and other endpoints.

  1. To evaluate disease-related symptoms and overall quality of life among patients receiving docetaxel only to those receiving docetaxel and ZD1839 (Iressa, gefitinib).

VI. To evaluate whether additional clinical benefit associated with ZD1839 (Iressa, gefitinib) can be detected as an improvement in patient-reported symptoms on the FACT Head and Neck Symptom Index (FHNSI)-10 and GP5.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to treatment with prior chemotherapy (pretreated vs untreated), Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), weight loss within the past 6 months (< 5% vs ≥ 5%), and prior cetuximab treatment (yes or no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive docetaxel intravenously (IV) over 30-60 minutes on days 1, 8, and 15 and oral placebo once daily on days 1-28.

Arm II: Patients receive docetaxel as in arm I and oral gefitinib once daily on days 1-28.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in arm I who have disease progression may receive single-agent oral gefitinib once daily until further disease progression (which is called step 2 in the study).

Quality of life is assessed at baseline, on days 15 and 28 of course 1, on day 28 of all subsequent courses, and at 2-4 weeks after completion of study treatment.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 330 patients (165 per treatment arm) will be accrued for this study within 31.5 months.

Being tested
docetaxel, placebo, gefitinib
Keywords
docetaxel, gefitinib, head and neck cancer
Medical subject headings
Head and Neck Neoplasms

What participants receive

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

  • docetaxelDrug

    Also called RP 56976, Taxotere, TXT

    Given IV

  • placeboOther

    Also called PLCB

    Given orally

  • gefitinibDrug

    Also called Iressa, ZD 1839

    Given orally

Study groups in NCT00088907
Study groupRoleWhat they receive
Arm I (docetaxel and placebo)Active comparatorPatients receive docetaxel intravenously (IV) over 30-60 minutes on days 1, 8, and 15 and oral placebo once daily on days 1-28.
Receives: Drug: docetaxel; Other: placebo
Arm II (docetaxel and gefitinib)ExperimentalPatients receive docetaxel as in arm I and oral gefitinib once daily on days 1-28. ZD1839 (Iressa, gefitinib) will be given at a dose of 250 mg (one tablet) orally each day starting on day 1 and continuing for days 1 to 28 of each cycle until progression. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in arm I who have disease progression may receive single-agent oral gefitinib once daily until further disease progression.
Receives: Drug: docetaxel; Drug: gefitinib

What is being measured

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

  1. Overall Survival

    Overall survival is defined as time from registration to death from any cause. All eligible and treated patients were included in the analysis.

    Measured: assessed every 3 months if patient is < 2 years from study entry then every 6 months if patient is 2-5 years from study entry. No specific requirements if patient is more than 5 years from study entry.

Secondary outcomes (2)

  1. Time to Progression

    Time to progression is defined as time from registration to disease progression. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions .

    Tumor measurements may be made using physical examination, CT scans or MRI scans. While on protocol treatment, tumor measurement by physical examination to be done every 4 weeks, and tumor measurement by CT/MRI scans to be done every 8 weeks (every 2 treatment cycles).

    All eligible and treated patients were included in the analysis.

    Measured: assessed every 3 months if patient is < 2 years from study entry then every 6 months if patient is 2-5 years from study entry. No specific requirements if patient is more than 5 years from study entry.

  2. Overall Response Rate

    Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Complete response (CR) was defined disappearance of all tumor lesions. Partial response (PR) was defined as as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. Overall response rate= CR+PR.

    Tumor measurements may be made using physical examination, CT scans or MRI scans. While on protocol treatment, tumor measurement by physical examination to be done every 4 weeks, and tumor measurement by CT/MRI scans to be done every 8 weeks (every 2 treatment cycles).

    All eligible and treated patients were included in the analysis.

    Measured: assessed every 3 months if patient is < 2 years from study entry then every 6 months if patient is 2-5 years from study entry. No specific requirements if patient is more than 5 years from study entry.

Timeline

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

  1. First posted5 Aug 2004 (estimated)
  2. Study startAug 2004
  3. Primary completionMay 2009
  4. Study completionAug 2012

Why it stopped: It was unlikely that the primary endpoint would be reached based on the fifth interim analysis results.

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
270 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00088907
Sponsor's protocol ID
NCI-2012-02956
Other IDs
ECOG-E1302, U10CA021115
Status last verified
Jul 2013
First submitted
4 Aug 2004
Last updated
6 May 2015
Data monitoring committee
Yes

Publications

  • Argiris A, Ghebremichael M, Gilbert J, Lee JW, Sachidanandam K, Kolesar JM, Burtness B, Forastiere AA. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013 Apr 10;31(11):1405-14. doi: 10.1200/JCO.2012.45.4272. Epub 2013 Mar 4.

    PubMed 23460714

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing docetaxel and gefitinib in people with Recurrent Head and Neck Cancer and Metastatic Head and Neck Cancer, 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 29 inclusion and 11 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 6 May 2015. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 6 May 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?

Overall Survival (time frame: assessed every 3 months if patient is < 2 years from study entry then every 6 months if patient is 2-5 years from study entry. No specific requirements if patient is more than 5 years from study entry.). 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 NCT00088907, 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 6 May 2015.

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