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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00088907
• Collaborator: (none)
• Enrollment: 270
• Location: 1
• Arms: 2
• Duration (Months): 96
• Patients Per Site Per Month: 2.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Head and Neck Cancer; Metastatic Head and Neck Cancer	Drug: docetaxel; Other: placebo; Drug: gefitinib	Phase 3

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).

2. 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.

3. 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.

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

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

6. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 270 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Outcome Measures

Primary Outcome Measures

1. Overall Survival [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 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

1. 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.]

   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.

2. 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.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Eastern Cooperative Oncology Group	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Athanassios Argiris, Eastern Cooperative Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00088907
• Other Study ID Numbers: NCI-2012-02956; ECOG-E1302; U10CA021115; NCT00695760
• First Posted: Aug 5, 2004
• Last Update Posted: May 6, 2015
• Last Verified: Jul 1, 2013

• Keywords provided by National Cancer Institute (NCI): docetaxel; gefitinib; head and neck cancer
• Additional relevant MeSH terms: Head and Neck Neoplasms; Docetaxel; Gefitinib

Study Results

Participant Flow

Recruitment Details	The study was activated on August 6,2004 and terminated on November 13,2008. A total of 270 patients (136 on arm I and 134 on arm II) was enrolled to first step of the study. In July 2007, registration to step 2 (single ZD1839 therapy) was suspended because other study indicated lack of good benefit/risk profile of single agent ZD1839.

Arm/Group Title	Arm I (Docetaxel and Placebo)	Arm II (Docetaxel and Gefitinib)
Arm/Group Description	Patients receive docetaxel intravenously (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. docetaxel: Given IV placebo: Given orally	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. docetaxel: Given IV gefitinib: 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.
Period Title: Randomized Study (Step 1)
STARTED	136	134
Treated	129	124
Eligible	117	122
Eligible and Treated	117	122
COMPLETED	0	0
NOT COMPLETED	136	134
Period Title: Randomized Study (Step 1)
STARTED	24	0
Treated	19	0
COMPLETED	0	0
NOT COMPLETED	24	0

Baseline Characteristics

Arm/Group Title	Arm I (Docetaxel and Placebo)	Arm II (Docetaxel and Gefitinib)	Total
Arm/Group Description	Patients receive docetaxel intravenously (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. docetaxel: Given IV placebo: Given orally	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. docetaxel: Given IV gefitinib: 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.	Total of all reporting groups
Overall Participants	117	122	239
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61	60	60
Sex: Female, Male (Count of Participants)
Female	25 21.4%	24 19.7%	49 20.5%
Male	92 78.6%	98 80.3%	190 79.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I (Docetaxel and Placebo)	Arm II (Docetaxel and Gefitinib)
Arm/Group Description	Patients receive docetaxel intravenously (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. docetaxel: Given IV placebo: Given orally	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. docetaxel: Given IV gefitinib: 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.
Measure Participants	117	122
Median (95% Confidence Interval) [months]	5.98	7.33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Docetaxel and Placebo), Arm II (Docetaxel and Gefitinib)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Time to Progression
Description	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.
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.

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I (Docetaxel and Placebo)	Arm II (Docetaxel and Gefitinib)
Arm/Group Description	Patients receive docetaxel intravenously (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. docetaxel: Given IV placebo: Given orally	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. docetaxel: Given IV gefitinib: 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.
Measure Participants	117	122
Median (95% Confidence Interval) [months]	2.14	3.55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Docetaxel and Placebo), Arm II (Docetaxel and Gefitinib)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Overall Response Rate
Description	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.
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.

Outcome Measure Data

Analysis Population Description

eligible and treated patients

Arm/Group Title	Arm I (Docetaxel and Placebo)	Arm II (Docetaxel and Gefitinib)
Arm/Group Description	Patients receive docetaxel intravenously (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. docetaxel: Given IV placebo: Given orally	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. docetaxel: Given IV gefitinib: 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.
Measure Participants	117	122
Number (95% Confidence Interval) [percentage of participants]	4.3 3.7%	9.8 8%

Adverse Events

Time Frame	Assessed every cycle (1 cycle = 4 weeks) while on treatment and for the 30 days following the last dose of protocol drug (which was included in the form for the last cycle).
Adverse Event Reporting Description	Prior to diagnosis of progression / relapse or after start of non-protocol therapy, severe (Grade ≥ 3) long term toxicity that has not been previously reported was included in the report as well.
Arm/Group Title	Step 1: Docetaxel+Placebo		Step 1: Docetaxel+ZD1839		Step 2: ZD1839
Arm/Group Description	Premedication: Dexamethasone Docetaxel as a 60 m inute infusion 35mg/m2 to be given on days 1,8,and 15 of a 28-day schedule Placebo one tablet daily orally starting on day 1. Treatment to continue from days 1-28 of each cycle.		Premedication: Dexamethasone Docetaxel as a 60 m inute infusion 35mg/m2 to be given on days 1,8, and 15 of a 28-day schedule. ZD1839 (Iressa, gefitinib) 250 mg/daily orally starting on day 1. Treatment to continue from days 1-28 of each cycle.		ZD1839 (Iressa, gefitinib) 250 mg/daily orally starting on day 1. Treatment to continue from days 1-28 of each cycle.
All Cause Mortality
	Step 1: Docetaxel+Placebo		Step 1: Docetaxel+ZD1839		Step 2: ZD1839
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Step 1: Docetaxel+Placebo		Step 1: Docetaxel+ZD1839		Step 2: ZD1839
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/129 (49.6%)		61/124 (49.2%)		2/19 (10.5%)
Blood and lymphatic system disorders
Anemia	5/129 (3.9%)		0/124 (0%)		0/19 (0%)
Febrile neutropenia	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Cardiac disorders
Atrial fibrillation	1/129 (0.8%)		1/124 (0.8%)		0/19 (0%)
Ventricular tachycardia	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Heart failure	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Gastrointestinal disorders
Diarrhea	3/129 (2.3%)		16/124 (12.9%)		0/19 (0%)
Dysphagia	1/129 (0.8%)		2/124 (1.6%)		1/19 (5.3%)
Colonic fistula	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Mucositis oral	0/129 (0%)		2/124 (1.6%)		0/19 (0%)
Mucositis oral	3/129 (2.3%)		2/124 (1.6%)		0/19 (0%)
Nausea	5/129 (3.9%)		7/124 (5.6%)		0/19 (0%)
Duodenal perforation	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Vomiting	4/129 (3.1%)		3/124 (2.4%)		0/19 (0%)
Intra-abdominal hemorrhage	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Esophageal hemorrhage	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Oral hemorrhage	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Abdominal pain	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
General disorders
Fatigue	21/129 (16.3%)		14/124 (11.3%)		1/19 (5.3%)
Sudden death NOS	0/129 (0%)		3/124 (2.4%)		0/19 (0%)
Edema face	1/129 (0.8%)		2/124 (1.6%)		0/19 (0%)
Edema limbs	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Non-cardiac chest pain	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Immune system disorders
Anaphylaxis	2/129 (1.6%)		1/124 (0.8%)		0/19 (0%)
Infections and infestations
Enterocolitis infectious	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Infections and infestations - Other, spe	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Infections and infestations - Other, spe	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Abdominal infection	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Catheter related infection	2/129 (1.6%)		0/124 (0%)		0/19 (0%)
Lung infection	9/129 (7%)		5/124 (4%)		0/19 (0%)
Soft tissue infection	1/129 (0.8%)		1/124 (0.8%)		0/19 (0%)
Skin infection	4/129 (3.1%)		1/124 (0.8%)		0/19 (0%)
Urinary tract infection	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Wound infection	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Lung infection	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Skin infection	1/129 (0.8%)		1/124 (0.8%)		0/19 (0%)
Sepsis	1/129 (0.8%)		3/124 (2.4%)		0/19 (0%)
Injury, poisoning and procedural complications
Injury to carotid artery	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Investigations
White blood cell decreased	5/129 (3.9%)		6/124 (4.8%)		0/19 (0%)
Lymphocyte count decreased	9/129 (7%)		4/124 (3.2%)		0/19 (0%)
Neutrophil count decreased	4/129 (3.1%)		4/124 (3.2%)		0/19 (0%)
Platelet count decreased	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Weight loss	2/129 (1.6%)		1/124 (0.8%)		0/19 (0%)
INR increased	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Activated partial thromboplastin time pr	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Alkaline phosphatase increased	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Alanine aminotransferase increased	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Creatinine increased	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Metabolism and nutrition disorders
Anorexia	3/129 (2.3%)		6/124 (4.8%)		0/19 (0%)
Dehydration	6/129 (4.7%)		8/124 (6.5%)		0/19 (0%)
Hypoalbuminemia	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Hyperglycemia	1/129 (0.8%)		2/124 (1.6%)		0/19 (0%)
Hypophosphatemia	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Hypokalemia	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Hyponatremia	3/129 (2.3%)		1/124 (0.8%)		0/19 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	1/129 (0.8%)		1/124 (0.8%)		0/19 (0%)
Generalized muscle weakness	6/129 (4.7%)		1/124 (0.8%)		0/19 (0%)
Trismus	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecif	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Nervous system disorders
Peripheral motor neuropathy	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Peripheral sensory neuropathy	0/129 (0%)		4/124 (3.2%)		0/19 (0%)
Syncope	0/129 (0%)		2/124 (1.6%)		0/19 (0%)
Headache	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Psychiatric disorders
Insomnia	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Renal and urinary disorders
Acute kidney injury	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Adult respiratory distress syndrome	1/129 (0.8%)		1/124 (0.8%)		0/19 (0%)
Bronchospasm	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Cough	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Dyspnea	6/129 (4.7%)		5/124 (4%)		0/19 (0%)
Hypoxia	2/129 (1.6%)		1/124 (0.8%)		0/19 (0%)
Pleural effusion	1/129 (0.8%)		2/124 (1.6%)		0/19 (0%)
Pneumonitis	3/129 (2.3%)		1/124 (0.8%)		0/19 (0%)
Respiratory, thoracic and mediastinal di	0/129 (0%)		0/124 (0%)		0/19 (0%)
Skin and subcutaneous tissue disorders
Nail loss	1/129 (0.8%)		1/124 (0.8%)		0/19 (0%)
Pruritus	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Rash maculo-papular	2/129 (1.6%)		0/124 (0%)		0/19 (0%)
Palmar-plantar erythrodysesthesia syndro	1/129 (0.8%)		0/124 (0%)		0/19 (0%)
Vascular disorders
Hypotension	3/129 (2.3%)		3/124 (2.4%)		0/19 (0%)
Thromboembolic event	0/129 (0%)		1/124 (0.8%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Step 1: Docetaxel+Placebo		Step 1: Docetaxel+ZD1839		Step 2: ZD1839
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/129 (12.4%)		25/124 (20.2%)		2/19 (10.5%)
Blood and lymphatic system disorders
Anemia	10/129 (7.8%)		16/124 (12.9%)		0/19 (0%)
Gastrointestinal disorders
Diarrhea	4/129 (3.1%)		7/124 (5.6%)		1/19 (5.3%)
Nausea	6/129 (4.7%)		11/124 (8.9%)		0/19 (0%)
General disorders
Fatigue	11/129 (8.5%)		14/124 (11.3%)		1/19 (5.3%)
Investigations
White blood cell decreased	4/129 (3.1%)		7/124 (5.6%)		0/19 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/129 (0%)		0/124 (0%)		1/19 (5.3%)
Alopecia	0/129 (0%)		0/124 (0%)		2/19 (10.5%)
Rash maculo-papular	0/129 (0%)		7/124 (5.6%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.