Know Cancer

forgot password

A Phase I Study of Sorafenib and RAD001 in Patients With Metastatic Renal Cell Carcinoma

Phase 1
21 Years
Open (Enrolling)
Renal Cell Carcinoma

Thank you

Trial Information

A Phase I Study of Sorafenib and RAD001 in Patients With Metastatic Renal Cell Carcinoma

Phase I of the study will be an open-label dose escalation study to determine the MTD of the
combination of sorafenib and RAD001. There will be a 7-day sorafenib run-in period prior to
starting of RAD001 during cycle 1 to determine the pharmacokinetic effect of adding RAD001
on sorafenib drug levels. Starting doses will be set at RAD001 2.5 mg PO QD and sorafenib
400mg PO BID, continuously. Cycle length will be 4 weeks. Between 3 and 18 patients will be
treated in the phase I portion of this study.

Inclusion Criteria:

1. Histologically- or cytologically-confirmed renal cell carcinoma containing
predominant (>50%) clear cell histology, which is metastatic or unresectable

2. Cytoreductive nephrectomy is allowed

3. Evidence of RECIST-defined measurable disease (lesions that can be accurately
measured in at least one dimension with the longest diameter ≥ 20mm using
conventional techniques or ≥10 mm with spiral CT scan)

4. Male or female at least 21 years old

5. ECOG performance status 0-1

6. Adequate bone marrow function:

1. ANC ≥ 1500/uL

2. platelet count ≥ 100,000/uL

3. hemoglobin ≥ 9.0 g/dL

7. Adequate hepatic function:

1. Total bilirubin ≤ 1.5 X ULN

2. AST (SGOT) ≤ 2.5 X ULN

3. ALT (SGPT) ≤ 2.5 X ULN

8. Adequate renal function as determined by either:

1. Calculated or measured creatinine clearance ≥ 40 mL/min (for calculated
creatinine clearance, Cockroft-Gault equation will be used) Modified
Cockcroft-Gault formula: ((140 - age(yrs)) x (actual weight(kg))) / (72 x serum

* Multiply by another factor of 0.85 if female

2. Serum creatinine ≤ 1.5 X ULN

9. Able to swallow oral medications

10. Resolution of any pre-existing toxicity from prior therapy to NCI CTCAE V3.0 ≤ grade

11. Signed and dated informed consent document

12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures

13. More than 28 days since any prior therapy, including investigational agents and
surgical procedures

Exclusion Criteria:

1. Collecting duct, papillary, or chromophobe type renal cell carcinoma without a clear
cell component are excluded. Transitional cell carcinoma of the renal pelvis is

2. No more than two prior systemic regimens for renal cell carcinoma

3. Phase I: No prior treatment with sorafenib. Phase II: No prior treatment with prior
anti-VEGF therapies, including sorafenib, sunitinib, thalidomide, or bevacizumab

4. No prior treatment with RAD001, CCI-779, or similar agents

5. Prior surgery, radiation therapy, or systemic therapy for renal cell carcinoma within
4 weeks of starting study treatment

6. History of or known brain metastasis, spinal cord compression, or carcinomatous
meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI

7. Any of the following within 12 months prior to study drug administration: myocardial
infarction, unstable or severe angina, coronary or peripheral artery bypass graft,
NYHA functional Class II, III, IV congestive heart failure, cerebrovascular accident
or transient ischemic attack, or pulmonary embolism

8. Hypertension that is unable to be controlled with medications

9. Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome
(AIDS)-related illness

10. "Currently active" second malignancy other than non-melanoma skin cancers. Patients
are not considered to have a "currently active" malignancy if they have completed
therapy and are considered to have a less than 30% risk of relapse

11. Current treatment on another clinical trial

12. Pregnant or breastfeeding

13. Chronic treatment with systemic steroids or other immunosuppressive agent

14. Patients with an active bleeding diathesis or on oral vitamin K antagonist medication
(except low dose warfarin)

15. History of malabsorption syndrome, disease significantly affecting gastrointestinal
function or major resection of stomach or small bowel that could interfere with
absorption, distribution, metabolism, or excretion of study drugs

16. Any serious and/or unstable pre-existing medical, psychiatric, or other condition
(including lab abnormalities) that could interfere with subject safety or obtaining
informed consent. Examples of such include uncontrolled diabetes, nonhealing wound,
severe infection, severe malnutrition, ventricular arrhythmias, active ischemic heart
disease, chronic liver or renal disease, or active upper GI tract ulceration -

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:


Safety Issue:


Principal Investigator

Charles Ryan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

October 2006

Completion Date:

December 2014

Related Keywords:

  • Renal Cell Carcinoma
  • RAD001
  • Sorafenib
  • Renal Cell Carcinoma
  • Metastatic
  • Carcinoma
  • Carcinoma, Renal Cell



University of California, San Francisco San Francisco, California  94143