Safety and Toxicity Study of Sorafenib in Patients With Kidney Cancer

A Phase 2 Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma at Stanford University

Determine time-to-progression (TTP) for an escalating dose schedule for subjects with progressive metastatic renal cell carcinoma treated with sorafenib

Study Overview

• Status: Completed
• Conditions: Kidney Cancer; Carcinoma, Renal Cell; Kidney Disease
• Intervention / Treatment: Drug: Sorafenib

Detailed Description

Sorafenib to be administered as 28-day cycles.

Sorafenib dose escalation by cycle is:

• Cycle 1: 400 mg BID
• Cycle 2: 600 mg BID
• Cycle 3+: 800 mg BID

Within subject dose escalation and maximum dose is dependent on observed tolerability.

Dose escalation only occurs after acceptable tolerability is demonstrated by subject.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Histologically- or cytologically-confirmed metastatic or unresectable renal cell carcinoma (RCC).
2. must have a component of conventional clear cell renal carcinoma.
3. No more than one prior systemic therapy.
4. No prior vascular endothelial growth factor receptor agents.
5. Prior palliative radiotherapy in metastatic lesion(s) is permitted, provided the subject has at least one measurable and/or evaluable lesion(s) that has not been irradiated.
6. All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to Day 1 dosing. Patients must have recovered from surgery and/or radiotherapy toxicity prior to Day 1 dosing.
7. Measureable disease by RECIST criteria
8. Karnofsky performance status at least 70% or ECOG not more than 2
9. Ability to give written informed consent
10. At least 18 years old
11. Negative pregnancy test within 7 days of Day 1 dosing (female subjects of childbearing potential)
12. Sexually active fertile subjects must agree to use an accepted method of contraception during the course of the study for 3 months thereafter.
13. ANC at least 1,500/uL
14. Platelet count at least 100,000/uL
15. AST/ALT not more than 2.5 times the upper limit of normal (ULN)
16. Alkaline phosphatase not more than 2.5 x ULN
17. Serum bilirubin not more than 1.5 x ULN
18. Amylase/Lipase within normal range
19. Urinalysis not more than 1+ protein
20. Serum creatinine not more than 1.5 x ULN
21. No active ischemia by ECG
22. Echocardiogram or MUGA ejection fraction at least 40%

Exclusion Criteria:

1. Ongoing hemoptysis
2. Cerebrovascular accident within 12 months
3. Peripheral vascular disease with claudication on less than 1 block
4. History of clinically significant bleeding
5. Malignancy with true papillary/sarcomatoid features without any clear cell component
6. Chromophobe
7. Oncocytoma
8. Collecting duct tumors
9. Transitional cell carcinoma
10. Deep venous thrombosis or pulmonary embolus within one year of consent
11. Ongoing need for full-dose oral or parenteral anticoagulation. Low dose coumadin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin is allowed
12. Subjects with evidence of current central nervous system (CNS) metastases
13. MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to Day 1 dosing
14. Significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, II or IV)
15. Angina pectoris requiring nitrate therapy
16. Myocardial infarction within the last 6 months
17. Uncontrolled hypertension (defined as blood pressure at least 160 mmHg systolic or at least 90 mmHg diastolic on medication)
18. Ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency). Topical and/or inhaled steroids are allowed.
19. Uncontrolled psychiatric disorder
20. Delayed healing of wounds, ulcers, and/or bone fractures
21. Prior malignancy (EXCEPTIONS: adequately-treated basal cell or squamous cell skin cancer or any other cancer for which chemotherapy has been completed > 5 years ago and from which the patient has been disease-free for > 5 years)
22. Pregnant
23. Currently lactating
24. Currently using St John's Wort (an herb)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib; Cycle 1: 400 mg BID sorafenib; Cycle 2: 600 mg BID sorafenib; Cycle 3+: 800 mg BID sorafenib	Drug: Sorafenib; Sorafenib administered in escalating 28-days cycles (400, 600 and 800 mg BID); Other Names: Nexavar; Sorafenib tosylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time-to-progression (TTP)	12 months

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: February 27, 2009
• First Submitted That Met QC Criteria: March 2, 2009
• First Posted (Estimate): March 3, 2009

Study Record Updates

• Last Update Posted (Estimate): June 19, 2015
• Last Update Submitted That Met QC Criteria: May 20, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Kidney Diseases; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: IRB-04988; 96919 (Other Identifier: Stanford Secondary IRB Approval Number); SU-02272009-1898 (Other Identifier: Stanford University); RENAL0009 (Other Identifier: OnCore)