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Iressa and Taxotere Study in Patients With Metastatic Urothelial Cancer

This study has been terminated.
(Study halted due to drug sponsor decision to not continue.)
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00479089
First received: May 24, 2007
Last updated: October 8, 2015
Last verified: September 2015
  Purpose

Primary Objective:

1. To compare the proportion of patients free from progression 9 months from the start of consolidation therapy with the combination of docetaxel and ZD1839 (Iressa) versus docetaxel alone. For the purposes of this protocol, "consolidation" therapy refers to treatment given at the time of maximal benefit from conventional front-line multi-agent chemotherapy.

Secondary Objective:

1. To compare time to progression (TTP), overall survival (OS) and cause-specific survival (CSS) in the two arms. For completeness, these will be reported both from the initiation of consolidation chemotherapy, and from the completion of induction chemotherapy.


Condition Intervention Phase
Bladder Cancer
Drug: Docetaxel
Drug: ZD1839
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Weekly Docetaxel (Taxotere) Vs. Weekly Docetaxel in Combination With ZD1839 (Iressa®) As Consolidation Therapy For Metastatic Urothelial Cancer Following Maximal Response To Multi-Agent Chemotherapy

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants Free From Progression 9 Months From Start of Consolidation Therapy [ Time Frame: Assessment at 9 Months of therapy ] [ Designated as safety issue: No ]
    The proportion of participants' progression free at 9 months compared between treatments using chi-square. Progressive disease was defined as at least a 25% increase from baseline, of the sum of the products of the two greatest dimensions of representative measurable lesions. Increasing severity in symptoms due to progressive tumor was also counted as progression even if they were not accompanied by an objective indicator on radiographic imaging. The development of any new measurable lesions was considered evidence of progressive cancer as well.


Secondary Outcome Measures:
  • Median Overall Survival [ Time Frame: Baseline till participant death or end of follow-up period, assessed every 4 weeks, up to 5 years. ] [ Designated as safety issue: No ]
    Overall survival was summarized using the Kaplan-Meier estimation.

  • Median Progression Free Survival From Trial Enrollment for Overall Study [ Time Frame: From trial enrollment to disease progression or death, up to five years ] [ Designated as safety issue: No ]
    Progressive disease was defined as at least a 25% increase from baseline, of the sum of the products of the two greatest dimensions of representative measurable lesions. Increasing severity in symptoms due to progressive tumor was also counted as progression even if they were not accompanied by an objective indicator on radiographic imaging. The development of any new measurable lesions was considered evidence of progressive cancer as well.


Enrollment: 50
Study Start Date: February 2004
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Weekly Docetaxel
Docetaxel 25 mg/m^2 IV over 30 minutes for 4 weeks with premedication with Dexamethasone, followed by 2 weeks off therapy.
Drug: Docetaxel
25 mg/m2 IV over 30 minutes for 4 weeks, followed by 2 weeks off therapy.
Other Name: Taxotere
Drug: Dexamethasone

Course #1: 3 doses of prophylactic Dexamethasone 4mg orally every 12 hours, starting the night before the Docetaxel infusion.

Course #2: If no hypersensitivity reactions and no significant fluid retention during course 1, the Dexamethasone is reduced to 4mg orally twice daily on the day of therapy.

Course #3 and subsequent courses: If no hypersensitivity reactions and no significant fluid retention during course 2, the Dexamethasone is reduced to 4mg orally one hour before treatment.

Active Comparator: Weekly Docetaxel + ZD1839
Docetaxel 25 mg/m^2 IV over 30 minutes for 4 weeks with premedication with Dexamethasone, followed by 2 weeks off therapy. ZD1839 250 mg by mouth daily, without break.
Drug: Docetaxel
25 mg/m2 IV over 30 minutes for 4 weeks, followed by 2 weeks off therapy.
Other Name: Taxotere
Drug: ZD1839
250 mg by mouth daily, without break.
Other Names:
  • Iressa
  • Gefitinib
Drug: Dexamethasone

Course #1: 3 doses of prophylactic Dexamethasone 4mg orally every 12 hours, starting the night before the Docetaxel infusion.

Course #2: If no hypersensitivity reactions and no significant fluid retention during course 1, the Dexamethasone is reduced to 4mg orally twice daily on the day of therapy.

Course #3 and subsequent courses: If no hypersensitivity reactions and no significant fluid retention during course 2, the Dexamethasone is reduced to 4mg orally one hour before treatment.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients must have histologic demonstration of metastatic or locally unresectable transitional cell carcinoma of the urothelium. Minor components (<50% overall) of variants such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid of small cell change are acceptable. However, when these atypical histologies are dominant, other treatment approaches may be appropriate, and such patients are not eligible.
  • All patients must have demonstrated some objective response to combination chemotherapy, and be clinically without progression since this response was appreciated. In general, patients will have been treated with at least two successive combination regimens in order to achieve maximum benefit from available chemotherapy.
  • Patients who have not achieved a complete response to therapy must have received one of the chemotherapy regimens outlined in Appendix D prior to receiving consolidation therapy. Exceptions to this generalization would include patients with a near complete response to the first regimen given, or patients that are not fit for aggressive chemotherapy beyond an initially used regimen to which they responded. Patients must begin "consolidation" therapy within 6 weeks of the end of the last cycle of induction chemotherapy, and should begin as soon as possible.
  • Zubrod performance status of 3 or better. If PS = 3 this must, in the opinion of the investigator, be secondary to the effects of induction chemotherapy and not the underlying cancer.
  • Patients with a history of cardiac disease, or an ejection fraction (EF) less than 50% at the time of initiation of chemotherapy, must be demonstrated to have an ejection fraction of at least 40%. In addition, patients having received more than 250 mg/m^2 of doxorubicin during their induction phase, or who have EKG changes since initiation of chemotherapy must have an EF of at least 45%. Patients with no history of cardiac disease, a normal EKG and no more than 250 mg/m^2 of doxorubicin are not required to have an EF measurement.
  • Provision of written informed consent.
  • Women of childbearing potential must be willing to practice acceptable methods of birth control to prevent pregnancy.
  • Males taking ZD1839 must also use birth control while taking the drug to avoid pregnancy in their partner.
  • International normalized ratio (INR) elevations, bleeding, or both events have been reported in some patients taking warfarin. Patients taking warfarin with a target INR of > or = 2, should be monitored regularly (every week in the first cycle, with further monitoring based on the experience in the first cycle) for changes in prothrombin time (PT) or INR. Patients on prophylactic low dose warfarin (ie: 1-2 mg qd for central line thrombosis prophylaxis) do not require frequent monitoring.

Exclusion Criteria:

  • Predominantly small cell histology.
  • AST or conjugated bilirubin greater than twice the upper limit of normal.
  • Serum creatinine greater than 2.5 mg/dL , or a creatinine clearance (either measured or estimated by Cockcroft formula) of less than 25 mL/min: creatinine clearance (CLcr) = [(140-age) x wt(kg)]/[72 xCreat (mg/dL)] (Multiply by 0.85 for females)
  • Absolute neutrophil count (ANC) less than 1,000; Platelets less than 75,000.
  • Prior (lifetime) cumulative exposure to doxorubicin greater than 400 mg/m^2.
  • Pregnant and lactating women are excluded. Women of childbearing potential must have a negative pregnancy test prior to starting therapy.
  • An active, or likely to become active, second malignancy.
  • Known severe hypersensitivity to ZD1839 or any of the excipients of this product.
  • Concomitant use of phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital of St. John's Wort
  • Treatment with a non-approved or investigational drug within 30 days before Day 1 of trial treatment.
  • Incomplete healing from previous oncologic or other major surgery
  • Note that there is no requirement for measurable or evaluable disease. Evaluation of response to therapy is not an endpoint of this trial.
  • Prior treatment with therapy which specifically targets the HER family of receptors.
  • Patients with peripheral neuropathy > or = to grade 2 should be excluded. Patients may be included if their neuropathy has resolved to grade 1 by the time they are registered on the protocol.
  • Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.
  • As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease).
  • Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded).
  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: NCT00479089

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
AstraZeneca
Investigators
Principal Investigator: Arlene Siefker-Radtke, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00479089     History of Changes
Other Study ID Numbers: 2003-0767  NCI-2010-00595 
Study First Received: May 24, 2007
Results First Received: July 27, 2015
Last Updated: October 8, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Transitional Cell Carcinoma
Urothelium
Urothelial Cancer
Bladder Cancer
Docetaxel
Taxotere
ZD1839
Gefitinib
Iressa
Consolidation Therapy

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Docetaxel
Gefitinib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 23, 2016