Gemcitabine and Split-dose Cisplatin (GC) Plus Sorafenib in Chemotherapy-naïve Patients With Locally Advanced or Metastatic Urothelial Carcinoma

NCT00714948 | Terminated Phase 2 Results

• 1 other identifier: 07-168
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Standard chemotherapy drugs generally work by killing rapidly dividing cells in your body. Cancers cells are some of the most rapidly dividing cells and that is why chemotherapy can be effective in some patients. Gemcitabine and Cisplatin are an effective and standard drug combination used to treat locally advanced and metastatic urothelial cancer. However, these drugs do not shrink tumors in all patients and when they do, it is generally for a limited amount of time. This has led scientists to look for different ways to treat cancer. New drugs have been developed to treat cancer that work differently than standard chemotherapy drugs. These drugs attempt to decrease the blood supply to tumors. By doing so, this may limit the tumor's source of oxygen and nutrients and prevent the tumor from growing. Sorafenib is an example of a drug that works in this way. In some patients with advanced kidney cancer, sorafenib alone has been shown to slow the progression of their disease. The purpose of this study is to find out what effects, good and/or bad, the combination of gemcitabine, cisplatin, and sorafenib has on you and your cancer.

Conditions

Bladder Cancer; URINARY BLADDER

Keywords

Bladder; Urinary; SORAFENIB; CISPLATIN; GEMCITABINE

Outcome Measures

Primary Outcomes (1)

• To Determine the Progression Free Survival Rate at One Year Untreated Patients With Advanced/Metastatic Urothelial Carcinoma Treated With the Combination of Sorafenib, Gemcitabine, and Cisplatin.

  conclusion of the study

Study Arms (1)

1

EXPERIMENTAL

This is a phase II trial of gemcitabine and Split-dose cisplatin plus sorafenib.

Drug: gemcitabine and cisplatin plus sorafenib

Interventions

gemcitabine and cisplatin plus sorafenib DRUG

Gemcitabine 1000 mg/m 2 will be administered on days 1 and 8 and cisplatin 35 mg/m 2 will be administered on days 1 and 8. A total of six cycles of therapy will be administered at 21day intervals. Sorafenib 400 mg PO twice daily will be initiated on day 1 of cycle 1 and continued, as tolerated, until the time of disease progression or a maximum of 12 months. The total chemotherapy dose for gemcitabine and cisplatin (GC) may be modified for patients with severe obesity (e.g. body surface area (BSA) \> 2.1), after consultation with the Principal Investigator.

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Eligibility Criteria

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

You may qualify if:

• Patients must have measurable or evaluable urothelial cancer.
• Measurable disease includes unresectable or metastatic urothelial tract tumors that are unidimensionally measurable by xray,CT/MRI scan or physical examination.
• Evaluable disease is restricted to patients with unresectable primary bladder tumors which can be evaluated for response by cystoscopy.
• Pathologic confirmation by the Department of Pathology at MSKCC.
• Karnofsky Performance Status (KPS) ≥60%.
• Adequate marrow function defined as granulocytes ≥ 1500 cells/mm 3 , platelets ≥ 100,000 cells/mm 3 , and hemoglobin ≥ 8.0 g/dl.
• Serum creatinine \< 2.0 mg/dl
• hour urine sample demonstrating creatinine clearance ≥ 60 ml/min/1.73m2 or calculated creatinine clearance ≥ 60 ml/min/1.73m 2 using the formula: Jeliffe Equation: estimated creatinine clearance = 98 x (0.8 \[age(yrs) 20\]/Serum Creatinine (mg/dL) x (0.9 if Female))
• Adequate hepatic function defined as:
• Total Bilirubin \< or = to 1.5 x ULN
• AST and ALT \< or = to 3.0 x ULN (\< or = to 5.0 x ULN is acceptable if liver has tumor involvement)
• Normal coagulation profile including PT/INR and PTT, unless patient is receiving anticoagulation therapy with agents such as warfarin or heparin.
• Age ≥ 18 years
• Informed consent
• Women of childbearing potential must have a negative pregnancy test.

You may not qualify if:

• Prior treatment with systemic chemotherapy (prior intravesical therapy is permitted).
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
• Blood Pressure of \> 150/100 mm Hg.
• Irradiation within 4 weeks of start of protocol.
• Evidence of another active cancer, except for nonmelanoma skin carcinoma, insitu carcinoma of the cervix curatively treated, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is nondetectable.
• Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris.
• History of a myocardial infarction within 6 months.
• History of a stroke or transient ischemic attack within 6 months.
• Clinically significant peripheral vascular disease.
• Evidence of bleeding diathesis or coagulopathy.
• Presence of central nervous system or brain metastases.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0.
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0.
• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0.
• Serious nonhealing wound, ulcer, or bone fracture.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bayer: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Gemcitabine; Cisplatin; Sorafenib

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Limitations and Caveats

Early termination leading to no subjects analyzed. Only two participants were enrolled and treated on this study. Neither completed the study as they both came off due to adverse events.

Results Point of Contact

• Title: Dr. Dean Bajorin
• Organization: Memorial Sloan Kettering Cancer Center

bajorind@mskcc.org

646-422-4333

Study Officials

• Matthew Milowsky, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 10, 2008
• First Posted: July 14, 2008
• Study Start: July 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: November 16, 2015
• Results First Posted: November 16, 2015

Record last verified: 2015-10

Locations

US (1)