Study of Docetaxel and Oxaliplatin in Metastatic Transitional Cell Cancer (TCC) of the Urothelial Tract

• ClinicalTrials.gov Identifier: NCT03159143
• Recruitment Status: Completed
• First Posted: May 18, 2017
• Results First Posted: August 11, 2017
• Last Update Posted: August 11, 2017
• Sponsor: Leonard Appleman
• Collaborator: Sanofi-Synthelabo
• Information provided by (Responsible Party): Leonard Appleman, University of Pittsburgh

Study Description

Brief Summary:

The purpose of this non-randomized Phase II trial was to evaluate the efficacy of a combination of docetaxel and oxaliplatin in patients with metastatic transitional cell cancer (TCC) of the urothelial tract. The primary endpoint was to assess response, as defined as a 25% reduction in measurable disease per the RECIST criteria. Measurable or evaluable objective response rate, time to disease progression and survival were also assessed.

Condition or disease	Intervention/treatment	Phase
Metastatic Transitional Cell Cancer of the Urothelial Tract	Drug: Docetaxel; Drug: Oxaliplatin	Phase 2

Detailed Description:

This non-randomized Phase II trial was to evaluate the efficacy of a combination of docetaxel and oxaliplatin in patients with metastatic transitional cell cancer (TCC) of the urothelial tract. The primary endpoint was to assess response, as defined as a 25% reduction in measurable disease per the RECIST criteria. Measurable or evaluable objective response rate, time to disease progression and survival were also assessed.

Treatment was administered on an outpatient basis. No other concurrent therapy for malignant disease was administered. Patients received both docetaxel and oxaliplatin, IV on day 1 of each cycle. Treatment will be repeated every 21 days for up to 6 courses in the absence of disease progression, unacceptable toxicity, or treatment delay > 3 weeks.

All patients should receive antiemetics prior to treatment. An oral or IV 5-HT3 receptor antagonist in combination with a benzodiazepene and Decadron was recommended. To mitigate docetaxel associated hypersensitivity reactions, Decadron was administered at a dose of 8mg bid, 1 day prior to, the day of, and the day after administration of docetaxel (total of 3 days)

Day 1 of each cycle:

Docetaxel was administered at a dose of 60mg/m2 IV infusion, followed by oxaliplatin at a dose of 110mg/m2 as a 2 hour IV infusion. Oxaliplatin solution was further diluted in an infusion solution of 250 mL to 500 mL Dextrose 5% in Water (D5W). Oxaliplatin was be capped at a maximum BSA of 2.0

Day 2 of each cycle:

Patients received growth factor support as needed. At the discretion of the investigator, patients were treated with both white and red cell growth factors. Generally, white cell support is recommended if patients experience a febrile neutropenia with the preceeding cycle, or are over the age of 70 yrs, and thought to be at a high risk of febrile neutropenia (74-76)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a non-randomized Phase II trial in metastatic transitional cell cancer (TCC) of the urothelial tract.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Single-arm Study of Docetaxel and Oxaliplatin in Metastatic Cisplatin-resistant Transitional Cell Carcinoma of the Urinary Bladder
• Actual Study Start Date: December 17, 2004
• Actual Primary Completion Date: June 2, 2009
• Actual Study Completion Date: December 2, 2009

Arms and Interventions

Arm

Intervention/treatment

Experimental: Docetaxel and Oxaliplatin; Docetaxel administered at a dose of 60mg/m^2 IV infusion, followed by oxaliplatin at a dose of 110mg/m^2 as a 2 hour IV infusion.

Drug: Docetaxel; Docetaxel (28) is a semi-synthetic taxane which blocks mitosis by preventing microtubule depolymerization. It mediates its actions by binding to a different set of microtubule-associated proteins than paclitaxel. It is administered every 3 weeks as a 30 minute infusion at doses between 60 to 75 mg/m^2.; Other Name: Taxotere; Drug: Oxaliplatin; Alkylating antineoplastic agent. It is administered on day 1 of each cycle at a dose of 110 mg/m^2

Outcome Measures

Primary Outcome Measures :

1. Response Rate [ Time Frame: Up to 4 years ]
   Percentage of patients who experienced a greater than or equal to a 30% reduction in measurable disease, as per the RECIST criteria.

Secondary Outcome Measures :

1. Time to Progression (TTP) [ Time Frame: Up to 4 years ]
   Time to progression (TTP) will be calculated as number of months from the date of first treatment to the date of disease progression or the date of death (disease-related causes) or the cut-off date.
2. Disease Control Rate (DCR) [ Time Frame: Up to 4 years ]
   Percentage of patients who achieved complete response, partial response and stable disease. DCR will be calculated from the first day of the first cycle to the date of metastatic or primary tumor relapse, or last contact date, or date of death (if death comes before disease progression), or data cut-off.
3. Overall Survival [ Time Frame: Up to 4 years ]
   The overall survival will be calculated as the number of months from the date of first treatment until death or the cut-off date.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed transitional cell carcinoma of the Urothelial tract.
• Confirmed metastatic disease.
• Measurable progressive disease is required.
• 18 years of age. Because no dosing or adverse event data are currently available on the use of oxaliplatin in patients < 18 years of age, they are excluded from this study.
• Life expectancy of greater than 6 months.
• ECOG Performance status of 0-1.
• Must have received prior treatment with standard of care chemotherapy No more than 2 prior regimens of cytotoxic chemotherapy.
• No other experimental treatment, cytotoxics or radiation 4 weeks prior to enrollment.
• Patients must have acceptable organ function as defined below:

Hematopoietic: WBC > 2500/mm3 or ANC > 1500/mm3, hemoglobin > 9.0 g/dL, platelet count > 100,000/mm3 Hepatic: Bilirubin < 1.5 mg/dL, SGOT/SGPT < 2 x ULN (< 4 x ULN if liver metastases present) Renal: Creatinine < 1.8 mg/dL

• Adequate neurologic function defined as no clinically significant peripheral neuropathy, defined as any neuropathy ≤ grade 1.
• Adequate cardiovascular function defined as no active congestive heart failure, no uncontrolled angina, no myocardial infarction within the past 6 months.

Exclusion Criteria:

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• No prior therapy with oxaliplatin is allowed.
• No history of allergic reactions attributed to the drugs used in this study or compounds of similar chemical or biologic composition.
• No history of intolerance or allergy to the antiemetics to be administered in conjunction with the study drugs (i.e., 5 HT3 antagonists).
• No concurrent other active cancer from another primary site, except squamous cell and basal cell carcinoma of the skin.
• No other serious concomitant illness will be allowed, including interstitial pneumonia, extensive and symptomatic fibrosis of the lung, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, NYHA Class III or IV, serious cardiac arrhythmia, uncontrolled diabetes mellitus or active infection.

Contacts and Locations

Locations

United States, Pennsylvania

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

Leonard Appleman

Sanofi-Synthelabo

Investigators

• Principal Investigator: Leonard Appleman, MD; Univesity of Pittsburgh

More Information

• Responsible Party: Leonard Appleman, Principal Investigator, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT03159143
• Other Study ID Numbers: UPCI 04-055
• First Posted: May 18, 2017
• Results First Posted: August 11, 2017
• Last Update Posted: August 11, 2017
• Last Verified: August 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Docetaxel; Oxaliplatin; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action