Phase III Randomized, Placebo Controlled, Trial Of Docetaxel Versus Docetaxel Plus ZD1839 (Iressa, Gefitinib, NSC 715055) In Performance Status 2 Or Previously Treated Patients With Recurrent Or Metastatic Head And Neck Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00088907
First received: August 4, 2004
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: docetaxel
Other: placebo
Drug: gefitinib
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 3

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival in poor prognosis SCCHN patients treated with docetaxel with or without ZD1839 (Iressa, gefitinib) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be performed using a one-sided log-rank test stratified on the 4 stratification factors.


Secondary Outcome Measures:
  • Time to progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Response rate assessed using the RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A two-sided Fisher's exact test with 5% type I error will be performed.

  • Quality of life [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Longitudinal data analysis will be performed to describe the change trend of the scores over time across the two treatments. The area under the QOL vs. time curve (AUC) over six months will be used as a summary measure to compare the two treatment arms.


Enrollment: 330
Study Start Date: August 2004
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (docetaxel and placebo)

Patients receive docetaxel IV over 30-60 minutes on days 1, 8, and 15 and oral placebo 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.

Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: Arm II (docetaxel and gefitinib)

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.

Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: gefitinib
Given orally
Other Names:
  • Iressa
  • ZD 1839
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088907

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Athanassios Argiris Eastern Cooperative Oncology Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088907     History of Changes
Obsolete Identifiers: NCT00695760
Other Study ID Numbers: NCI-2012-02956, E1302, ECOG-E1302, U10CA021115
Study First Received: August 4, 2004
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Tongue Neoplasms
Carcinoma, Verrucous
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Laryngeal Neoplasms
Paranasal Sinus Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Salivary Gland Diseases
Otorhinolaryngologic Neoplasms
Respiratory Tract Neoplasms
Nose Neoplasms

ClinicalTrials.gov processed this record on July 31, 2014