Sorafenib in Treating Patients With Metastatic Kidney Cancer That Has Not Responded to Sunitinib or Bevacizumab

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00866320
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 49
• Locations: 2
• Arm: 1
• Duration (Months): 46
• Patients Per Site: 24.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with metastatic kidney cancer that has not responded to sunitinib or bevacizumab.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Drug: sorafenib tosylate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the tumor burden reduction rate in patients with sunitinib malate- or bevacizumab-refractory, metastatic clear cell renal cell carcinoma treated with sorafenib tosylate.

Secondary

• To determine the safety of sorafenib tosylate in these patients.

• To record the duration of tumor reduction, time to disease progression, and overall survival of patients treated with sorafenib tosylate.

OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma (RCC) Refractory to SU11248 or Bevacizumab Therapy
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib Chemotherapy single agent systemic. Sorafenib given up to 600mg orally every 12 hours for up to 10 months (40 weeks).	Drug: sorafenib tosylate; Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor targeting both tumor cells and the tumor vasculature. Patients with metastatic RCC meeting eligibility criteria will receive 400 mg BID of sorafenib in a single-arm phase II study. Treatment will be administered on an outpatient basis.

Outcome Measures

Primary Outcome Measures

1. Tumor Burden Reduction Rate (TBRR) [at 8 weeks (2cycles of treatment)]

   The primary endpoint of the study is defined as the percentage of patients who experience larger than or equal to 5% reduction in tumor burden as measured by RECIST-defined target lesions without progression of non-target lesions or the appearance of any new lesions, confirmed at least 4 weeks after first documentation. RECIST criteria will be used for the purpose of designating target lesions, calculating total tumor burden (the sum of the unidimensional measurement of target lesions) and defining disease progression.Additional RECIST-defined partial or complete responses will be recorded.

Secondary Outcome Measures

1. Overall Survival [followed until progression or death for approximately 3 years]

   Overall survival measured in months and summarized using the Kaplan-Meier method. This will be calculated from the date of registration on-study to the dates of documented evidence of progression and death, respectively.

2. Time to Progression [followed to progression for approximately 3 years]

   Time to objective progression will be measured from the start of treatment until the criteria for RECIST-defined progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. Progression-free survival measured in months and summarized using the Kaplan-Meier method.

3. Duration of Overall Response (Tumor Burden Reduction) [followed for overall response for approximately 3 years]

   Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma with a component of clear cell histology

• Metastatic disease

• Disease progression, as defined by RECIST criteria, after prior treatment with sunitinib malate or bevacizumab

• Patients must have received ≥ 1 course (4 weeks) of sunitinib malate or ≥ 2 doses of bevacizumab AND have RECIST-defined objective progression during or within 4 months after completing treatment with sunitinib malate or bevacizumab

• Measurable disease by RECIST criteria

• CNS metastases allowed provided patient has undergone prior surgery and/or radiotherapy AND has no evidence of further CNS disease progression by CT scan or MRI ≥ 2 weeks after treatment of CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%

• WBC ≥ 3,000/μL

• Absolute neutrophil count ≥ 1,500/μL

• Platelet count ≥ 75,000/μL

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST/ALT ≤ 2.5 times ULN

• Creatinine ≤ 2.0 times ULN

• Negative pregnancy test

• No significant cardiovascular disease, including any of the following:

• Congestive heart failure (New York Heart Association class III-IV heart disease)

• Active angina pectoris requiring nitrate therapy

• Uncontrolled dysrhythmias

• Cardiovascular event within the past 6 months (e.g., transient ischemic attack/cerebrovascular accident, myocardial infarction, or vascular surgery)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 2 weeks since prior systemic therapy, radiotherapy, or major surgery and recovered

• No prior sorafenib tosylate

• No other concurrent investigational agents

• No other concurrent anticancer therapy

• No concurrent prophylactic growth factors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
2	Baylor Sammons Cancer Center	Dallas	Texas	United States	75246

Sponsors and Collaborators

• Case Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Brian I. Rini, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00866320
• Other Study ID Numbers: CASE11805; P30CA043703; CASE11805; 05-167
• First Posted: Mar 20, 2009
• Last Update Posted: Jul 23, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Case Comprehensive Cancer Center: clear cell renal cell carcinoma; recurrent renal cell cancer; stage IV renal cell cancer
• Additional relevant MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell; Sorafenib

Study Results

Participant Flow

Recruitment Details	This is a multiple site study. Patients were recruited 2/2006-4/2008 from medical hospitals in Cleveland, Ohio and Dallas, Texas

Arm/Group Title	Sorafenib
Arm/Group Description	Patients receive Sorafenib 400 mg BID until disease progression or toxicity. Dose may be escalated to 600mg and 800 mg BID after the 8 week disease reassessment.
Period Title: Overall Study
STARTED	49
COMPLETED	43
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Sorafenib
Arm/Group Description	Patients receive Sorafenib 400 mg BID until disease progression or toxicity. Dose may be escalated to 600mg and 800 mg BID after the 8 week disease reassessment.
Overall Participants	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (8.1)
Sex: Female, Male (Count of Participants)
Female	36 73.5%
Male	13 26.5%
Region of Enrollment (participants) [Number]
United States	49 100%

Outcome Measures

1. Primary Outcome

Title	Tumor Burden Reduction Rate (TBRR)
Description	The primary endpoint of the study is defined as the percentage of patients who experience larger than or equal to 5% reduction in tumor burden as measured by RECIST-defined target lesions without progression of non-target lesions or the appearance of any new lesions, confirmed at least 4 weeks after first documentation. RECIST criteria will be used for the purpose of designating target lesions, calculating total tumor burden (the sum of the unidimensional measurement of target lesions) and defining disease progression.Additional RECIST-defined partial or complete responses will be recorded.
Time Frame	at 8 weeks (2cycles of treatment)

Outcome Measure Data

Analysis Population Description

All patients who started treatment

Arm/Group Title	Sorafenib
Arm/Group Description	Patients receive sorafenib twice a day until disease progression or toxicity.
Measure Participants	47
Achieved at least 5% tumor reduction	30
Did not achieve at least 5% tumor reduction	70

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival measured in months and summarized using the Kaplan-Meier method. This will be calculated from the date of registration on-study to the dates of documented evidence of progression and death, respectively.
Time Frame	followed until progression or death for approximately 3 years

Outcome Measure Data

Analysis Population Description

All patients who started treatment

Arm/Group Title	Sorafenib
Arm/Group Description	Patients receive sorafenib twice a day until disease progression or toxicity.
Measure Participants	47
Median (95% Confidence Interval) [months]	16

3. Secondary Outcome

Title	Time to Progression
Description	Time to objective progression will be measured from the start of treatment until the criteria for RECIST-defined progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. Progression-free survival measured in months and summarized using the Kaplan-Meier method.
Time Frame	followed to progression for approximately 3 years

Outcome Measure Data

Analysis Population Description

All patients who started treatment

Arm/Group Title	Sorafenib
Arm/Group Description	Sorafenib twice a day until progression or toxicity
Measure Participants	47
Median (95% Confidence Interval) [months]	4.4

4. Secondary Outcome

Title	Duration of Overall Response (Tumor Burden Reduction)
Description	Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Time Frame	followed for overall response for approximately 3 years

Outcome Measure Data

Analysis Population Description

Patients who achieved at least 5% tumor reduction

Arm/Group Title	Sorafenib
Arm/Group Description	Patients receive Sorafenib twice a day until disease progression or toxicity
Measure Participants	14
Median (95% Confidence Interval) [months]	7.1

Adverse Events

Time Frame	Adverse events collected from the start of treatment to the end of the study for a period of 3 years and 8 months.
Arm/Group Title	Sorafenib
Arm/Group Description	Patients receive Sorafenib 400 mg BID until disease progression or toxicity. Dose may be escalated to 600mg and 800 mg BID after the 8 week disease reassessment.
All Cause Mortality
	Sorafenib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	4/47 (8.5%)
Cardiac disorders
Thrombosis/embolism	1/47 (2.1%)
Gastrointestinal disorders
Anorexia	1/47 (2.1%)
Constipation	1/47 (2.1%)
Nausea	1/47 (2.1%)
General disorders
Constitutional Symptoms	1/47 (2.1%)
Pain	1/47 (2.1%)
Metabolism and nutrition disorders
Metabolic/Laboratory	1/47 (2.1%)
Musculoskeletal and connective tissue disorders
Myalgia (muscle pain)	1/47 (2.1%)
Skin and subcutaneous tissue disorders
Hand-Foot Skin Reaction	1/47 (2.1%)
Other (Not Including Serious) Adverse Events
	Sorafenib
	Affected / at Risk (%)	# Events
Total	41/47 (87.2%)
Blood and lymphatic system disorders
Hemoglobin	4/47 (8.5%)
Endocrine disorders
Hypothyroidism	4/47 (8.5%)
Gastrointestinal disorders
Anorexia	17/47 (36.2%)
Constipation	5/47 (10.6%)
Diarrhea	25/47 (53.2%)
Taste Disturbance (dysgeusia)	7/47 (14.9%)
Nausea	13/47 (27.7%)
Stomatitis/pharyngitis	13/47 (27.7%)
Vomiting	6/47 (12.8%)
Gastrointestinal-other	11/47 (23.4%)
General disorders
Edema	4/47 (8.5%)
Fatigue	25/47 (53.2%)
Fever	3/47 (6.4%)
Rigors, Chills	3/47 (6.4%)
Weight Loss	10/47 (21.3%)
General Disorders-other	3/47 (6.4%)
Pain-other	9/47 (19.1%)
Musculoskeletal and connective tissue disorders
Musculoskeletal-other	4/47 (8.5%)
Arthralgia	4/47 (8.5%)
Myalgia (muscle pain)	5/47 (10.6%)
Nervous system disorders
Headache	4/47 (8.5%)
Reproductive system and breast disorders
Voice Changes/stridor/larynx	4/47 (8.5%)
Respiratory, thoracic and mediastinal disorders
Cough	4/47 (8.5%)
Dyspnea	3/47 (6.4%)
Skin and subcutaneous tissue disorders
Alopecia	12/47 (25.5%)
Rash/desquamation	14/47 (29.8%)
Dry Skin	6/47 (12.8%)
Hand-Foot Skin Reaction	28/47 (59.6%)
Dermatology/Skin-other	14/47 (29.8%)
Vascular disorders
Hypertension	16/47 (34%)

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.