Carcinoma, Renal Cell, Kidney Cancer, Kidney Disease
Conditions
Brief summary
Determine time-to-progression (TTP) for an escalating dose schedule for subjects with progressive metastatic renal cell carcinoma treated with 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.
Interventions
DRUGSorafenib
Sorafenib administered in escalating 28-days cycles (400, 600 and 800 mg BID)
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time-to-progression (TTP) | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib * Cycle 1: 400 mg BID sorafenib
* Cycle 2: 600 mg BID sorafenib
* Cycle 3+: 800 mg BID sorafenib
Sorafenib: Sorafenib administered in escalating 28-days cycles (400, 600 and 800 mg BID) | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Sorafenib |
|---|---|
| Age, Continuous | 60 years |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Time-to-progression (TTP)
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib | Time-to-progression (TTP) | 5.3 months |