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

This study has been terminated.
(It was unlikely that the primary endpoint would be reached based on the fifth interim analysis results.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00088907
First received: August 4, 2004
Last updated: April 21, 2015
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
Recurrent Head and Neck Cancer
Metastatic Head and Neck Cancer
Drug: docetaxel
Other: placebo
Drug: gefitinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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 [ 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. ] [ Designated as safety issue: No ]
    Overall survival is defined as time from registration to death from any cause. All eligible and treated patients were included in the analysis.


Secondary Outcome Measures:
  • Time to Progression [ 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. ] [ Designated as safety issue: No ]

    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.


  • Overall Response Rate [ 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. ] [ Designated as safety issue: No ]

    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.



Enrollment: 270
Study Start Date: August 2004
Study Completion Date: August 2012
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 intravenously (IV) over 30-60 minutes on days 1, 8, and 15 and oral placebo once daily on days 1-28.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: placebo
Given orally
Other Name: PLCB
Experimental: Arm II (docetaxel and gefitinib)

Patients 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.

Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Drug: gefitinib
Given orally
Other Names:
  • Iressa
  • ZD 1839

  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 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
  • 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

Exclusion criteria:

  • 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
  • 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
  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

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088907     History of Changes
Obsolete Identifiers: NCT00695760
Other Study ID Numbers: NCI-2012-02956, ECOG-E1302, U10CA021115
Study First Received: August 4, 2004
Results First Received: March 20, 2015
Last Updated: April 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
docetaxel
gefitinib
head and neck cancer

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Docetaxel
Gefitinib
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on July 01, 2015