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

NCT00088907 | Terminated Phase 3 Results DMC

• 3 other identifiers: NCI-2012-02956ECOG-E1302U10CA021115
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Recurrent Head and Neck Cancer; Metastatic Head and Neck Cancer

Keywords

docetaxel; gefitinib; head and neck cancer

Outcome Measures

Primary Outcomes (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.

  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)

• Time to Progression

  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.

• Overall Response Rate

  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.

Study Arms (2)

Arm I (docetaxel and placebo)

ACTIVE COMPARATOR

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; Other: placebo

Arm II (docetaxel and gefitinib)

EXPERIMENTAL

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; Drug: gefitinib

Interventions

docetaxel DRUG

Given IV

Also known as: RP 56976, Taxotere, TXT

Arm I (docetaxel and placebo); Arm II (docetaxel and gefitinib)

placebo OTHER

Given orally

Also known as: PLCB

Arm I (docetaxel and placebo)

gefitinib DRUG

Given orally

Also known as: Iressa, ZD 1839

Arm II (docetaxel and gefitinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 23460714 RESULT

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Docetaxel; Gefitinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG Statistical Office

617-632-3012

Study Officials

• Athanassios Argiris

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2004
• First Posted: August 5, 2004
• Study Start: August 1, 2004
• Primary Completion: May 1, 2009
• Study Completion: August 1, 2012
• Last Updated: May 6, 2015
• Results First Posted: May 6, 2015

Record last verified: 2013-07

Locations

US (1)