Iressa and Taxotere Study in Patients With Metastatic Urothelial Cancer

NCT00479089 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2003-0767NCI-2010-00595
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Transitional Cell Carcinoma; Urothelium; Urothelial Cancer; Bladder Cancer; Docetaxel; Taxotere; ZD1839; Gefitinib; Iressa; Consolidation Therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants Free From Progression 9 Months From Start of Consolidation Therapy

  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.

  Assessment at 9 Months of therapy

Secondary Outcomes (2)

• Median Overall Survival

  Baseline till participant death or end of follow-up period, assessed every 4 weeks, up to 5 years.

• Median Progression Free Survival From Trial Enrollment for Overall Study

  From trial enrollment to disease progression or death, up to five years

Study Arms (2)

Weekly Docetaxel

ACTIVE COMPARATOR

Docetaxel 25 mg/m\^2 IV over 30 minutes for 4 weeks with premedication with Dexamethasone, followed by 2 weeks off therapy.

Drug: Docetaxel; Drug: Dexamethasone

Weekly Docetaxel + ZD1839

ACTIVE COMPARATOR

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; Drug: ZD1839; Drug: Dexamethasone

Interventions

Docetaxel DRUG

25 mg/m2 IV over 30 minutes for 4 weeks, followed by 2 weeks off therapy.

Also known as: Taxotere

Weekly Docetaxel; Weekly Docetaxel + ZD1839

ZD1839 DRUG

250 mg by mouth daily, without break.

Also known as: Iressa, Gefitinib

Weekly Docetaxel + ZD1839

Dexamethasone DRUG

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.

Weekly Docetaxel; Weekly Docetaxel + ZD1839

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Docetaxel; Gefitinib; Dexamethasone

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Arlene Siefker-Radtke, MD/Associate Professor, Genitourinary Medical Oncology
• Organization: The University of Texas (UT) MD Anderson Cancer Center

[email protected]

713-792-2830

Study Officials

• Arlene Siefker-Radtke, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2007
• First Posted: May 25, 2007
• Study Start: February 1, 2004
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: November 2, 2015
• Results First Posted: October 6, 2015

Record last verified: 2015-09

Locations

US (1)