A Phase I/II Study of Sorafenib and Palliative Radiotherapy in Patients With Advanced Renal Cell Carcinoma and Symptomatic Bony Metastases
1. Eligible patients must have histologically or cytologically confirmed metastatic RCC
that is judged to be incurable with standard therapy.
2. Patients must have at least one radiographically-evident symptomatic (> 2/10 on the
Brief Pain Inventory) bone metastasis that is amenable to palliative radiation.
Multiple symptomatic bone metastases may be irradiated at the same time. However, if
more than one symptomatic bone metastasis is identified, one will be chosen as the
index lesion for reporting purposes.
3. No planned change in analgesic medications.
4. No planned increase in regular analgesic medications.
5. No prior surgery to the index lesion, although previous surgery for other metastatic
disease is permissible if > 4 weeks prior to study registration.
6. Patients may have had up to two previous lines of systemic treatment for metastatic
RCC, including prior treatment with sorafenib or another similar multi-targeted
tyrosine kinase inhibitor, if completed >4 weeks prior to study registration.
7. Patients may not have had previous radiotherapy to the index lesion. Patients may
have had previous radiotherapy to other metastases if completed > 4 weeks prior to
study registration. Patients must have recovered from the acute side effects of
radiotherapy prior to study registration.
8. Age >18 years.
9. Life expectancy of greater than 3 months.
10. ECOG performance status < 2 (Karnofsky > 60).
11. Patients must have normal organ and marrow function as defined below:
i. Absolute neutrophil count >1.5 x109 /L ii. Platelet count >75 x109 /L iii.
Total bilirubin < 1.5 x ULN iv. AST (SGOT) / ALT (SGPT) < 2.5 × institutional ULN
or < 5 x institutional ULN if liver metastases v. Creatinine <1.7 x ULN or vi.
Creatinine clearance > 50 mL/min/1.73 m2 vii. International Normalized Ratio (INR) <
1.5 viii. Hemoglobin value Hb > 80 g/L ix. Serum phosphate level > 0.80 mmol/L x.
Serum lipase, normal values (range of 5-208 U/L) xi. Serum amylase, normal values
(range 30-110 U/L)
12. Ability to understand and the willingness to sign a written informed consent
13. The effects of sorafenib on the developing human fetus at the recommended therapeutic
dose are unknown. Women of child-bearing potential must agree to use adequate
contraception prior to study entry and for the duration of study participation.
Effective methods of birth control would include a barrier method (e.g. condoms,
diaphragm) combined with spermicide, or an intrauterine device (IUD). Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.
1. Serious medical condition that might be aggravated by treatment, including but not
limited to: myocardial infarction within 6 months, congestive heart failure, unstable
angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled
hypertension, uncontrolled psychotic disorders, serious infections, active peptic
ulcer disease, active liver disease, or cerebrovascular disease with previous stroke.
2. Patients may not be receiving any other investigational agent concurrently or within
4 weeks of study registration. Patients receiving other molecularly-targeted
treatments for RCC off of study, including inhibitors of angiogenesis or mTOR, will
be eligible for this study after a 1 week wash-out period.
3. Patients with clinical or radiological evidence of spinal cord compression are
4. Patients who are at high risk of pathologic fracture and appropriate for surgical
intervention are ineligible.
5. Patients who are planned for palliative surgical intervention to the index lesion or
adjacent bone are ineligible.
6. Pregnant or lactating women are excluded from this study because the safety of
sorafenib has not been established in these circumstances.
7. Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with sorafenib.
8. Patients with other active malignancies other than non-melanoma skin cancer are
9. Patients who have had significant surgical procedures requiring a general anaesthetic
(for example, open laparotomy or thoracotomy) within the past month
10. Patients who possess significant unhealed wounds or ulcers
11. Patients with any bleeding or clotting disorder
12. Patient taking greater than 325mg of aspirin per day
13. Patients with diabetes mellitus will be ineligible for the PET-CT components of the
study, but will remain eligible to receive sorafenib.
14. Patients who are currently taking rifampin, phenytoin, carbamazepine, Phenobarbital,
dexamethasone and St. John's Wort.