Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00588666
• Collaborator: (none)
• Enrollment: 51
• Locations: 6
• Arm: 1
• Duration (Months): 67
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Gemcitabine and carboplatin are two standard chemotherapy drugs used to treat tumors of the urothelial tract. 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. One new class of drugs are called 'angiogenesis-inhibitors'. 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. Bevacizumab is an anti-angiogenic drug.

In some other cancers such as colon cancer and lung cancer, combining bevacizumab with standard chemotherapy shrinks tumors in a greater proportion of patients and makes patients live longer than using standard chemotherapy alone. This has never been tested in urothelial cancer and we do not know if bevacizumab will have the same effects in this disease. The purpose of this study is to find out what effects, good and/or bad, the combination of gemcitabine, carboplatin, and bevacizumab has on you and your cancer.

Condition or Disease	Intervention/Treatment	Phase
Myeloproliferative Disorder; Urothelial Carcinoma; Cancer	Drug: Bevacizumab; Drug: Carboplatin; Drug: Gemcitabine	Phase 2

Detailed Description

This is a phase II trial of gemcitabine, carboplatin, and bevacizumab in chemotherapy naïve patients with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Bevacizumab, Carboplatin, Gemcitabine Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.

Drug: Bevacizumab; Drug: Carboplatin; Drug: Gemcitabine

Outcome Measures

Primary Outcome Measures

1. Evaluate the Time to Disease Progression [3 years]

   Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI, 92(3):205-216, 2000]. Changes in only the largest diameter (uni-dimensional measurement) are used in the RECIST criteria.

Secondary Outcome Measures

1. The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC. [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologic documentation: diagnosis of transitional cell carcinoma of the bladder,urethra, ureter, or renal pelvis.

• Unresectable or metastatic disease

• Ineligible for cisplatin (or incurable with cisplatin)

• ≥ 4 weeks since prior RT

• Karnofsky Performance Status ≥ 60%

• Age ≥ 18 years of age

• Required Initial Laboratory Values: Absolute neutrophil count ≥ 1.2 x 109/L; Platelets ≥ 100 x 109/L; Bilirubin ≤ 1.5 times the upper limit of normal (x ULN) for the institution; Aspartate transaminase (AST) and alanine transaminase(ALT) ≤ 3.0 x ULN;Serum creatinine < 2.0 or calculated creatinine clearance (CrCl) ≥ 30 mL/min

Exclusion Criteria:

• 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 other than a Genentech-sponsored bevacizumab cancer study

• Blood pressure of >150/100 mmHg

• Unstable angina

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• History of myocardial infarction within 6 months

• History of stroke 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

• Anticipation of need for major surgical procedure during the course of the study

• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0

• Pregnant (positive pregnancy test) or lactating

• Albuminuria as demonstrated by a urinary albumin of greater or = to 1.0 g/24 hr at screening

• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 6 months prior to Day 0

• Serious, non-healing wound, ulcer, or bone fracture

• Inability to comply with study and/or follow-up procedures

• History of persistent gross hematuria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Cancer Center	Basking Ridge	New Jersey	United States
3	Memorial Sloan-Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
4	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
5	Memorial Sloan-Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York	United States	11570
6	Memoral Sloan Kettering Cancer Center@Phelps	Sleepy Hollow	New York	United States

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Dean Bajorin, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering web site

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00588666
• Other Study ID Numbers: 06-006
• First Posted: Jan 8, 2008
• Last Update Posted: Jan 22, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: Myeloproliferative Disorder; urinary bladder; Cancer; ureter; renal pelvis; chemotherapy
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Myeloproliferative Disorders; Gemcitabine; Bevacizumab; Carboplatin

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Period Title: Overall Study
STARTED	51
COMPLETED	47
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Overall Participants	51
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 29.4%
>=65 years	36 70.6%
Sex: Female, Male (Count of Participants)
Female	14 27.5%
Male	37 72.5%
Region of Enrollment (participants) [Number]
United States	51 100%

Outcome Measures

1. Primary Outcome

Title	Evaluate the Time to Disease Progression
Description	Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI, 92(3):205-216, 2000]. Changes in only the largest diameter (uni-dimensional measurement) are used in the RECIST criteria.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Measure Participants	47
Time to Progression	6.5
Overall Survival	13.9

2. Secondary Outcome

Title	The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Measure Participants	47
Number [percentage of participants]	49 96.1%

Adverse Events

Arm/Group Title	Treatment
Arm/Group Description	Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	29/51 (56.9%)
Blood and lymphatic system disorders
Febrile neutropenia	2/51 (3.9%)	2
Anemia	1/51 (2%)	1
Cardiac disorders
Myocardial ischemia	1/51 (2%)	1
Gastrointestinal disorders
Constipation	2/51 (3.9%)	2
Dysphagia	1/51 (2%)	1
Nausea	1/51 (2%)	1
Duodenal ulcer	1/51 (2%)	1
Vomiting	1/51 (2%)	1
General disorders
Death	1/51 (2%)	1
Fatigue	1/51 (2%)	1
Hemorrhage/Bleeding, other	1/51 (2%)	1
Chest pain	1/51 (2%)	1
Hepatobiliary disorders
Cholecystitis	1/51 (2%)	1
Hepatobiliary disease	1/51 (2%)	1
Infections and infestations
Abdominal infection	1/51 (2%)	1
Bladder infection	2/51 (3.9%)	2
Tooth infection	1/51 (2%)	1
Urinary tract infection	1/51 (2%)	1
Injury, poisoning and procedural complications
Injury, poisoning, and procedural complications-other, specify-device complication	2/51 (3.9%)	2
Vascular access complication	1/51 (2%)	1
Investigations
White blood cell decreased	1/51 (2%)	1
Lipase increased	1/51 (2%)	1
Neutrophil count decrease	1/51 (2%)	1
Platelet count decrease	2/51 (3.9%)	3
Musculoskeletal and connective tissue disorders
Fracture	1/51 (2%)	1
Muscle weakness	1/51 (2%)	1
Back pain	1/51 (2%)	1
Neck pain	1/51 (2%)	1
Nervous system disorders
Syncope	1/51 (2%)	1
Renal and urinary disorders
Renal and urinary disorders-other, specify-Renal failure	3/51 (5.9%)	3
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/51 (2%)	1
Vascular disorders
Thrombosis/thrombus/embolism	8/51 (15.7%)	8
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	15/51 (29.4%)
Gastrointestinal disorders
Nausea	3/51 (5.9%)	6
General disorders
Fatigue	11/51 (21.6%)	30
Investigations
Weight loss	4/51 (7.8%)	6
Vascular disorders
Thrombosis/thrombus/embolism	4/51 (7.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.