Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer

Bladder Cancer Clinical Trial

Official title:

A Phase II Trial of Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer: Hoosier Oncology Group GU04-75

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00234494
• Other study ID #: HOG GU04-75
• Status: Completed
• Phase: Phase 2
• First received: October 5, 2005
• Last updated: February 16, 2016
• Start date: November 2005
• Est. completion date: December 2008

Study information

• Verified date: February 2016
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Cisplatin is a very important agent for the treatment of TCC as it has a single agent response rate of approximately 15%. However, it has been most important as a part of combination chemotherapy, MVAC initially and now in combination with gemcitabine. Single agent gemcitabine has demonstrated an overall response rate (ORR) of approximately 25%, including some complete responses (CR), with minimal toxicity in patients with advanced bladder cancer. Bevacizumab, a murine anti-human VEGF monoclonal antibody, has been advanced for use in combination with cytotoxic chemotherapy to delay time to disease progression in patients with metastatic solid tumors.

This trial is designed to further assess the efficacy, safety and tolerability of this regimen in this patient population.

Description:

OUTLINE: This is a multi-center study.

• Cisplatin 70 mg/m2 Day 1

• Gemcitabine 1250 mg/m2 Day 1 and 8

• Bevacizumab 15 mg/kg Day 1

Review toxicity every cycle (every 3 weeks) Review for radiographic response every 2 cycles (every six weeks)

Progressive disease = off protocol therapy

Patients will be treated for up to a maximum of 8 cycles of cisplatin and gemcitabine (24 weeks of therapy). If a patient has not progressed by the end of 24 weeks (completion of cisplatin and gemcitabine), then patient will be treated with bevacizumab at 15 mg/kg every three weeks for a maximum of 12 months of bevacizumab therapy (since study entry).

If at any time patient has undue toxicity or progressive disease, patient will be removed from the study and followed until progression and for survival.

If the patient has Grade 3 or 4 neurotoxicity and/or the creatinine rises above 2.0, then the cisplatin will be discontinued and the patient continued on study and treated with gemcitabine and bevacizumab at the same dose and schedule.

ECOG Performance Status 0 or 1

Hematopoietic:

• White blood cell count > 3000/mm3

• Absolute neutrophil count (ANC) > 1500 mm/3

• Platelet count > 100,000/mm3

• Hemoglobin > 8 g/dL (may be transfused or receive erythropoietin support to maintain or exceed this level).

• INR < 1.5

• No full dose/therapeutic anticoagulation with either low molecular weight heparin or unfractionated heparin or coumadin

Hepatic:

• Total bilirubin of <1.5 mg/dL

• ALT <5 times upper limit of normal for subjects with documented liver metastases; <2.5 times the upper limit of normal for subjects without evidence of liver metastases.

Renal:

• Serum creatinine of < 1.5 mg/dL.

• Urine protein:creatinine ratio < 1.0 at screening

Cardiovascular:

• No history of myocardial infarction or stroke within the last 6 months

• No uncontrolled hypertension (blood pressure of >160 systolic and/or 110 diastolic mmHg on medication)

• No unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure

• No unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or clinically significant peripheral vascular disease.

Pulmonary:

• Not specified

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Previously untreated or relapsed locally advanced or metastatic transitional cell carcinoma of the bladder. (Patients with pathology showing ANY component of non-transitional cell histology are not eligible).

• Relapsed patients may have received prior chemotherapy = one year prior to study registration as part of a neoadjuvant or adjuvant regimen and must not have had intervening therapy from the end of that treatment until study entry.

• Measurable disease as per RECIST.

• Prior radiation therapy, immunotherapy, cytokine, biologic or vaccine therapy must be greater than 28 days prior to being registered for protocol therapy,

Exclusion Criteria:

• No known central nervous system metastasis. (imaging of brain only required if clinically indicated)

• No prior organ allograft.

• No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.

• No evidence of bleeding diathesis or coagulopathy.

• No history of serious, non-healing wound, ulcer or bone fracture

• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to being registered for protocol therapy.

• No prior history of malignancy in the past 5 years with the exception of basal cell and squamous cell carcinoma of the skin. Other cancers with low potential for metastasis, such as in situ cancers (e.g., Grade 1, TA TCC (low grade superficial bladder cancer), colonic polyp with focus of adenocarcinoma) can also be enrolled after approval from the study chair.

• No major surgical procedure, open biopsy, or significant traumatic injury less than 28 days prior to being registered for protocol therapy.

• Patients are not eligible if the need for any major surgical procedure is anticipated during the course of the study.

• Any minor surgical procedures, fine needle aspirations or core biopsies must be greater than 7 days prior to being registered for protocol therapy except procedures to secure a vascular access device which must be greater than 7 days prior to the start of protocol therapy.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer

Intervention

Drug:
• Cisplatin
Cisplatin 70 mg/m2, day 1
• Gemcitabine
Gemcitabine 1250 mg/m2, day 1 and 8
• Bevacizumab
Bevacizumab 15mg/kg, day 1

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Oncology Hematology Associates of SW Indiana	Evansville	Indiana
United States	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana
United States	Medical & Surgical Specialists, LLC	Galesburg	Illinois
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Quality Cancer Center (MCGOP)	Indianapolis	Indiana
United States	Arnett Cancer Care	Lafayette	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Siteman Cancer Center	St. Louis	Missouri
United States	AP&S Clinic	Terre Haute	Indiana

Sponsors (5)

Lead Sponsor	Collaborator
Christopher Sweeney, MBBS	Eli Lilly and Company, Genentech, Inc., Hoosier Cancer Research Network, Walther Cancer Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hahn NM, Stadler WM, Zon RT, Waterhouse D, Picus J, Nattam S, Johnson CS, Perkins SM, Waddell MJ, Sweeney CJ; Hoosier Oncology Group. Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoos — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	- To determine the progression free survival of patients with metastatic transitional cell cancer treated with cisplatin, gemcitabine and bevacizumab.	36 months	No
Secondary	Overall Survival Time	To estimate overall survival time in months.	36 months	No
Secondary	Estimate Response Rates	To estimate rate of partial response (PR), complete response (CR) and overall response (PR plus CR).	36 months	No
Secondary	Duration of Response for Responding Patients	To estimate duration of response for responding patients.	36 months	No

External Links

•   Hoosier Cancer Research Network Homepage