Phase II Study of 2-Methoxyestradiol Nanocrystal Colloidal Dispersion Alone and in Combination With Sunitinib Malate in Patients With Metastatic Renal Cell Carcinoma Progressing on Sunitinib Malate
1. Patients must have a histologically confirmed renal cell cancer with a component of
clear cell carcinoma and evidence of metastasis (pure sarcomatoid variant cancers and
collecting duct malignancies will be excluded).
2. Patients must have measurable disease, defined as at least one target lesion that can
be accurately measured in at least one dimension (longest diameter to be recorded) as
greater than or equal to 20 mm with conventional techniques or as greater than or
equal to 2 times the slice width with spiral CT scan (i.e. 10 mm if the CT slice
width is 5 mm, 14 mm if the CT slice width is 7 mm).
3. Patients must have previously received or be currently receiving sunitinib malate
(Sutent) with evidence of disease progression while receiving sunitinib malate (as
evident by new lesions on CT/MRI/bone scan or unequivocal growth in measurable tumor
Note: Patients will be stratified to:
A: Patients previously treated with sunitinib malate. At least 4 week washout since
last treatment administered is required before patient is eligible for study. Once
patients meet all other eligibility criteria, they will be treated with Panzem® NCD
B: Patients currently still on sunitinib. Patients will continue to receive their
current dose/schedule of sunitinib. Once eligibility determined, patients will be
started on Panzem® NCD concurrently with their sunitinib. No drug washout of
sunitinib malate is required for this stratification.
Note: Enrollment to the individual stratification will stop once that
stratification has met its accrual goal.
4. Age greater than or equal to 18 years.
5. Life expectancy of greater than 3 months.
6. ECOG performance status 0-2 (see Appendix A).
7. Patients must have normal organ and marrow function as defined below:
- leukocytes greater than or equal to 3,000/μL
- absolute neutrophil count greater than or equal to 1,200/μL
- hemoglobin greater than or equal to 9.0 g/dl (patient may be transfused to this
- platelets greater than or equal to 100,000/μL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT)less than or equal to 2.5 X institutional upper limit of
- creatinine less than or equal to 1.5 x institutional upper limit of normal
8. Adequate cardiac function by history. If the patient has any history of cardiac
disease (prior myocardial infarction, congestive heart failure, etc.), a normal
echocardiogram or multigated acquisition (MUGA) scan will be required (LVEF greater
than or equal to institutional lower limit of normal).
9. No evidence for uncontrolled hypertension as documented by 2 baseline blood pressure
readings taken at least 1 hour apart. The systolic blood pressure must be less than
or equal to 140 mmHg and the diastolic blood pressure less than or equal to 90 mmHg.
Patients are allowed to be on anti-hypertensive medications.
10. Ability to understand and the willingness to sign a written informed consent
1. No major surgery, radiotherapy, chemotherapy, cytokine therapy or other experimental
therapy is permitted within 4 weeks of treatment initiation. Patients must recover
to baseline or grade 1 from any clinically significant adverse event experienced
during those prior therapies.
2. Patients may not be concurrently receiving any other investigational agents while
participating on this study.
3. Patients with active brain metastases are excluded. Previously treated brain
metastasis will be allowed provided that the patient is clinically stable (off
systemic steroids and not on antiepileptic agents) with a repeat imaging study
(within 4 weeks of registration) of the brain confirming stable CNS disease. Patients
with known CNS carcinomatosis or leptomeningeal spread of their disease will be
excluded from this study due to their poor prognosis.
4. Patients with gastrointestinal abnormalities including inability to take oral
medications, requirement for intravenous alimentation, and malabsorption syndromes
will be excluded.
5. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
7. Patients with type I insulin-dependent diabetes or poorly-controlled type II
insulin-dependent diabetes or a fasting blood glucose of more than 10 mmol/L (200
mg/dL) will be excluded due to difficulty evaluating the tumor metabolic activity
8. History of myocardial infarction or hospitalization for congestive heart failure
within 12 months of enrollment.
9. History of prior malignancy (except basal cell carcinoma resected with curative
intent) unless resected or treated with curative intent, and disease free for greater
than or equal to 5 years.