A Phase II Trial of Gemcitabine, Capecitabine, and Bevacizumab in Metastatic Renal Cell Carcinoma

• Sponsor: University of Chicago (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00523640
• Collaborator: Genentech, Inc. (Industry), Eli Lilly and Company (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 73
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to find out what effects (good and bad) the combination of the chemotherapy drugs gemcitabine, capecitabine, and bevacizumab has on a patient and kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell	Drug: combination of gemcitabine, capecitabine, and bevacizumab	Phase 2

Detailed Description

• to determine the objective response rate and estimate the time to progression of combination gemcitabine, capecitabine, and bevacizumab in patients with metastatic clear cell renal cell cancer;

• to determine survival of combination gemcitabine, capecitabine, and bevacizumab in patients with metastatic cell renal cell cancer;

• to determine the toxicity of combination gemcitabine, capecitabine, and bevacizumab in patients with metastatic renal cell cancer;

• to collect baseline serum and plasma samples for exploration of possible prognostic and predictive markers

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Gemcitabine, Capecitabine, and Bevacizumab in Metastatic Renal Cell Carcinoma
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I Combination of gemcitabine, capecitabine, and bevacizumab gemcitabine 1000 mg/m^2 d1, 8, capecitabine 1000 mg (flat dose) po bid d1-14, and bevacizumab 15 mg/kg d 1, on a 21 day cycle	Drug: combination of gemcitabine, capecitabine, and bevacizumab; gemcitabine 1000 mg/m^2 d1, 8, capecitabine 1000 mg (flat dose) po bid d1-14, and bevacizumab 15 mg/kg d 1, on a 21 day cycle

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate [12 weeks]

   Per RECIST Criteria (V1.0) using standard cross-sectional CT scanning: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Response (R)= CR + PR.

2. Progression-free Survival [60 months]

   Progression is defined as a measurable increase in the sum of longest diameters of all target lesions, or unequivocable progression of non-target lesions, or the appearance of new lesions, since baseline

Secondary Outcome Measures

1. Overall Survival [60 months]

   Time from enrollment until death from any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic clear cell renal cell cancer

• Measurable disease

• Age 18 or older

• ECOG performance status of 0 - 1

• Blood pressure less than 140/90 on 2 separate occasions not more than 6 weeks prior to enrollment and not less than 24 hours apart

• Normal organ function

• Women of child-bearing potential and men must agree to use adequate contraception

• Ability to understand and the willingness to sign a written informed consent document and to follow all required study procedures

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients may not have had prior treatment with pyrimidine analogs or VEGF binding agents

• Patients may not be receiving any other investigational or therapeutic agents

• Patients may not be receiving therapeutic anticoagulation with warfarin, its congeners, heparin, low molecular weight heparinoids, specific thrombin inhibitors, or other similar agents Patients receiving low dose coumadin (1 mg daily) for central line patency are eligible

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment start, or anticipation of need for major surgical procedure during the course of the study Fine needle aspirations or core biopsies within 7 days prior to treatment start are acceptable

• Serious, nonhealing wound, ulcer, or bone fracture

• Evidence of bleeding diathesis or coagulopathy

• Patients with known brain metastases

• Uncontrolled intercurrent illness

• Pregnant women

• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• Genentech, Inc.
• Eli Lilly and Company

Investigators

• Principal Investigator: Walter Stadler, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00523640
• Other Study ID Numbers: 13662A
• First Posted: Aug 31, 2007
• Last Update Posted: Feb 11, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by University of Chicago: metastatic; renal cell; kidney; neoplasm
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Gemcitabine; Bevacizumab; Capecitabine

Study Results

Participant Flow

Recruitment Details	30 patients were enrolled in the trial between March 2005 and May 2008

Arm/Group Title	Combination of Gemcitabine, Capecitabine, and Bevacizumab
Arm/Group Description	combination of gemcitabine, capecitabine, and bevacizumab
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Combination of Gemcitabine, Capecitabine, and Bevacizumab
Arm/Group Description	combination of gemcitabine, capecitabine, and bevacizumab
Overall Participants	29
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	5 17.2%
Male	24 82.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.4%
White	28 96.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	29 100%
Performance Status (participants) [Number]
0	5 17.2%
1	23 79.3%
2	1 3.4%
Number of metastatic disease sites (participants) [Number]
1	2 6.9%
2	6 20.7%
3 or more	21 72.4%
Tumor histology (participant) [Number]
Clear cell	23
Poorly differentiated/unclassified	6
Fuhrman grade (participants) [Number]
1	0 0%
2	2 6.9%
3-4	21 72.4%
Unknown	6 20.7%
Prognostic risk group (participants) [Number]
Favorable	7 24.1%
Intermediate	19 65.5%
Poor	3 10.3%
Prior therapy-Nephrectomy (participants) [Number]
Yes	24 82.8%
No	5 17.2%
Prior therapy-Radiotherapy (participants) [Number]
Yes	15 51.7%
No	14 48.3%
Prior therapy-Cytokine therapy (participants) [Number]
Yes	8 27.6%
No	21 72.4%
Prior therapy-Oral Vascular Endothelial Growth Factor (VEGF) receptor kinase inhibitor (participants) [Number]
Yes	20 69%
No	9 31%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate
Description	Per RECIST Criteria (V1.0) using standard cross-sectional CT scanning: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Response (R)= CR + PR.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination of Gemcitabine, Capecitabine, and Bevacizumab
Arm/Group Description	combination of gemcitabine, capecitabine, and bevacizumab
Measure Participants	29
Number [proportion]	0.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Combination of Gemcitabine, Capecitabine, and Bevacizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion responding
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; 0.10 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Progression-free Survival
Description	Progression is defined as a measurable increase in the sum of longest diameters of all target lesions, or unequivocable progression of non-target lesions, or the appearance of new lesions, since baseline
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination of Gemcitabine, Capecitabine, and Bevacizumab
Arm/Group Description	combination of gemcitabine, capecitabine, and bevacizumab
Measure Participants	29
Median (95% Confidence Interval) [months]	5.3

3. Secondary Outcome

Title	Overall Survival
Description	Time from enrollment until death from any cause.
Time Frame	60 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination of Gemcitabine, Capecitabine, and Bevacizumab
Arm/Group Description	combination of gemcitabine, capecitabine, and bevacizumab
Measure Participants	29
Median (95% Confidence Interval) [months]	9.8

Adverse Events

Time Frame	Adverse events were monitored over the course of treatment
Adverse Event Reporting Description	Reported are numbers of patients with grade 3 or higher toxicity National Cancer Institute Common Toxicity Criteria (version 3.0) were used to assess and report adverse events
Arm/Group Title	Combination of Gemcitabine, Capecitabine, and Bevacizumab
Arm/Group Description	combination of gemcitabine, capecitabine, and bevacizumab
All Cause Mortality
	Combination of Gemcitabine, Capecitabine, and Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Combination of Gemcitabine, Capecitabine, and Bevacizumab
	Affected / at Risk (%)	# Events
Total	5/29 (17.2%)
Blood and lymphatic system disorders
Pulmonary Embolism/Deep Vein Thrombosis	3/29 (10.3%)
Gastrointestinal disorders
Bowel perforation	1/29 (3.4%)
Infections and infestations
Sepsis	1/29 (3.4%)
Nervous system disorders
Seizure	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Combination of Gemcitabine, Capecitabine, and Bevacizumab
	Affected / at Risk (%)	# Events
Total	20/29 (69%)
Blood and lymphatic system disorders
Leukopenia	5/29 (17.2%)
Neutropenia	9/29 (31%)
Anemia	4/29 (13.8%)
thrombocytopenia	2/29 (6.9%)
Gastrointestinal disorders
Nausea	2/29 (6.9%)
Emesis	2/29 (6.9%)
General disorders
Fatigue	6/29 (20.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/29 (6.9%)
Skin and subcutaneous tissue disorders
Hand foot syndrome	2/29 (6.9%)

Limitations/Caveats

Trial was designed with a maximum target accrual of 55 patients. The trial was halted early because emerging data with VEGF inhibitors challenged clinical relevance of the study and availability of multiple therapies challenged accrual.

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.