| Eligibility |
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy
that is not responsive to standard therapies or for which there is no effective
therapy.
- Expansion Cohort Phase: Histologically or cytologically confirmed recurrent serous or
clear cell epithelial ovarian adenocarcinoma, fallopian tube carcinoma, or primary
peritoneal carcinoma for which there is no available curative standard therapy, in the
investigator's opinion.
- Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.
- Life expectancy of at least 12 weeks.
- Ability to swallow and retain oral medication.
- Adequate organ system function.
- Male patients willing to use adequate contraceptive measures.
- Female patients who are not of child-bearing potential, and female patients of
child-bearing potential who agree to use adequate contraceptive measures and who have
a negative serum or urine pregnancy test within 24 hours prior to initial trial
treatment.
- Patients must have measurable or evaluable disease.
- Expansion Cohort Phase: Patients with serous histology must have a CA 125 level = 2x
ULN within 14 days prior to the start of X-82. Patients with elevated CA 125 levels at
baseline are not required to have measurable disease by RECIST criteria. Patients with
clear cell histology that do not have an elevated CA 125 level must have measurable
disease.
- Patients must be = 18 years of age.
- Patients entering this study must be willing to provide tissue from a previous tumor
biopsy (if available) for correlative testing. If tissue is not available, a patient
will still be eligible for enrollment into the study. For the expansion cohort,
patients will also be requested, but not required, to undergo a pre-treatment biopsy.
- Willingness and ability to comply with trial and follow-up procedures.
- Ability to understand the nature of this trial and give written informed consent.
Exclusion Criteria:
- Patients currently receiving cancer therapy (i.e., chemotherapy, radiation therapy,
immunotherapy, biologic therapy, hormonal therapy [with the exception of LHRH agonists
for prostate cancer], surgery and/or tumor embolization).
- Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter)
prior to the first dose of X-82. A minimum of 10 days between termination of the
investigational drug and administration of X-82 is required. In addition, any
drug-related toxicity should have recovered to grade 1 or less.
- Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited
palliative radiation is allowed =2 weeks). Chemotherapy regimens with delayed toxicity
within the last 4 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin
C). Chemotherapy regimens given continuously or on a weekly basis with limited
potential for delayed toxicity within the last 2 weeks.
- Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically
related to X-82 (sunitinib, sorafenib or pazopanib) or to the active ingredient of
X-82.
- Concomitant use of drugs with a risk of causing prolonged QTc and/or Torsades de
Pointes.
- Concomitant use of herbal medications (i.e. St. John's wort, Kava, ephedra (ma huang),
ginko biloba) at least 7 days prior to the first dose of study drug and throughout
participation in the trial.
- Patients with known CNS metastases, unless metastases are treated and stable and the
patients do not require systemic steroids
- Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose
of 1mg allowed for port line patency permitted). Low molecular weight heparin (LMWH)
will be allowed.
- Females who are pregnant or breastfeeding.
- Presence of active gastrointestinal (GI) disease or other condition that will
interfere significantly with the absorption, distribution, metabolism, or excretion of
X-82.
- Decreased left ventricular function at study entry defined as LVEF <50% by either
Echocardiogram or MUGA scan.
- Patients who have previously experienced myocardial infarction, severe/unstable
angina, coronary/peripheral arterial bypass, symptomatic congestive heart failure (New
York Heart Association [NYHA] Class 3 or 4), arterial thrombosis, cerebrovascular
accident, or transient ischemia, in the 60 days prior to Day 1 of Cycle 1.
- Patients with inadequately controlled hypertension (defined as BP > 150/100) with or
without current antihypertensive medications. Patients with a history of additional
risk factors for Torsades de Pointes (e.g. familial long QT syndrome, heart failure,
left ventricular hypertrophy, slow heart rate (<45 bpm).
- Patient with a QTcF interval =450 msecs or other significant ECG abnormalities as
determined the investigator.
- A serious active infection at the time of treatment, or another serious underlying
medical condition that would impair the ability of the patient to receive protocol
treatment.
- Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.
- Concurrent condition that in the investigator's opinion would jeopardize compliance
with the protocol
- Inability or unwillingness to comply with study and/or follow-up procedures outlined
in the protocol
- Patients with a history of intolerance to, or significant toxicity with, VEGFR
tyrosine kinase inhibitor(s) (TKI).
- Patients entering the expansion after the determination of MTD are limited to previous
treatment with one anti-VEGFR TKI
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