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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


Phase 3
18 Years
N/A
Not Enrolling
Both
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Salivary Gland Squamous Cell Carcinoma, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Salivary Gland Cancer, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Tongue Cancer, Untreated Metastatic Squamous Neck Cancer With Occult Primary

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Trial Information

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


PRIMARY OBJECTIVES:

I. 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:

I. To determine the time to progression, response rate, and quality of life parameters 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 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, TGF-alpha, Ki-67, ERK, p-ERK, p70s6, p- p70s6 , and p27.

III. To evaluate the frequency of common polymorphisms of 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.

V. 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 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),
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 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.

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.


Inclusion Criteria:



- Histologically or cytologically confirmed squamous cell carcinoma of the head and
neck; patient must not have nasopharyngeal carcinoma of histologic types 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 therapy with docetaxel at any time (even if part of prior curative treatment

- 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 be receiving any other investigational agent while on the study

- Patients must have either:

- Strata A:

- ECOG performance status 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

- No unstable systemic disease, including active infection, uncontrolled hypertension,
unstable angina, congestive heart failure, or serious arrhythmia requiring medication

- Absolute neutrophil count (ANC) >= 1500 /mm^3

- Platelets >= 100,000 /mm^3

- Hemoglobin >= 8.0 g/dl

- Bilirubin within normal limits

- Alkaline phosphatase, SGOT (AST), and SGPT

- Creatinine < 2.0 or creatinine clearance of > 60 ml/min

- No hypercalcemia related to head and neck cancer

- No known brain metastasis

- Females should not be 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

- 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 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

- No current peripheral neuropathy >= grade 2 at time of randomization

- Patients must not have any co-existing condition that would preclude full compliance
with the study

- No known hypersensitivity to ZD1839 (Iressa, gefitinib) or any excipients of this
product; no prior history of severe hypersensitivity reaction to Docetaxel or other
drugs formulated with polysorbate 80

- Drugs that are 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

- HIV positive patient's receiving combination anti-retroviral therapy are excluded
from the study because of possible pharmacokinetic interactions with ZD1839 (Iressa,
gefitinib)

- Patients may not have had tumor-related hemorrhagic events in the previous three
months that required as major medical intervention, such as surgery or embolization

- Patients must not be on therapeutic anticoagulation or have tumors that are
unequivocally invading major vessels (e.g. carotid artery)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Outcome Measure:

Overall survival in poor prognosis SCCHN patients treated with docetaxel with or without ZD1839 (Iressa, gefitinib)

Outcome Description:

Will be performed using a one-sided log-rank test stratified on the 4 stratification factors.

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Athanassios Argiris

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02956

NCT ID:

NCT00088907

Start Date:

August 2004

Completion Date:

Related Keywords:

  • Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Salivary Gland Cancer
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Verrucous Carcinoma of the Larynx
  • Recurrent Verrucous Carcinoma of the Oral Cavity
  • Salivary Gland Squamous Cell Carcinoma
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IVA Salivary Gland Cancer
  • Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVA Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Verrucous Carcinoma of the Larynx
  • Stage IVA Verrucous Carcinoma of the Oral Cavity
  • Stage IVB Salivary Gland Cancer
  • Stage IVB Squamous Cell Carcinoma of the Larynx
  • Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVB Squamous Cell Carcinoma of the Oropharynx
  • Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Verrucous Carcinoma of the Larynx
  • Stage IVB Verrucous Carcinoma of the Oral Cavity
  • Stage IVC Salivary Gland Cancer
  • Stage IVC Squamous Cell Carcinoma of the Larynx
  • Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVC Squamous Cell Carcinoma of the Oropharynx
  • Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Verrucous Carcinoma of the Larynx
  • Stage IVC Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Untreated Metastatic Squamous Neck Cancer With Occult Primary
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Tongue Neoplasms
  • Carcinoma, Verrucous
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

Eastern Cooperative Oncology GroupBoston, Massachusetts  02215