Subjects will be asked to participate in this clinical trial to examine the safety of
2-deoxyglucose (an agent which is quite similar to glucose) in the treatment of solid tumors
and hormone refractory prostate cancer. This agent works by blocking the metabolism of
glucose in the cells of the body. Although all cells require glucose for metabolism, it is
believed that cancer cells require significantly more glucose than normal cells to grow.
Therefore, even slight effects of glucose metabolism in cancer cells might result in the
shrinkage of certain cancers. This agent has been given to humans before and has only
caused mild nausea, vomiting and glucopenia (low blood sugar) at the doses given in these
studies. This study will further examine the safety of 2-deoxyglucose in the treatment of
advanced solid tumors and hormone refractory prostate cancer. The information obtained in
this study will be used to design future clinical studies with 2-deoxyglucose. Subjects
will be asked to take an oral solution of 2-deoxyglucose daily, by mouth, while on this
study. They will be asked to have CT Scans, Bone Scans, and optional PET (Positron Emission
Tomography) Scans prior to starting this study. PET scans will also be performed shortly
after the start of the study and after 2 cycles (6 weeks) of therapy. Subjects will be
asked to have a comprehensive physical examination and blood work prior to the start of the
study. During the first 2 cycles of the study subjects will be asked to have blood drawn at
different time intervals for the first 2 days of each cycle. While on the study, they will
be asked to return to the clinic at intervals of 1 week for a physical examination and blood
tests. Subjects will also be asked to have CT Scans and Bone Scans at intervals of 9 weeks
while on the study.
- Patients with any histologically proven metastatic solid tumor malignancy, without a
standard option of therapy will be eligible for the Phase I portion of this trial.
Patients with prostate cancer with metastatic disease, and progression after initial
hormonal therapy will be eligible for both the Phase I and II portion of this trial.
Phase II patients must have either measurable disease or a PSA value > 5 ng/ml.
- Patients with prostate cancer in whom bicalutamide or flutamide has been recently
withdrawn, must demonstrate progression of disease and be at least 6 weeks and 4
weeks respectively beyond the discontinuation of such agents. LHRH agonists will be
- Age >18 years and an estimated life expectancy of at least 6 months.
- ECOG performance status < 2. (see Appendix B)
- Patients must be ³ 4 weeks since last prior therapy (including surgery, chemotherapy,
radiation therapy). All previous clinically significant treatment-related toxicities
have resolved to less than or equal to Grade 1.
- An ANC >1500/µl, hemoglobin > 10 g/dl, and platelet count >100,000/µl are required.
- Adequate renal function (serum creatinine < 1.5 mg/dL or creatinine clearance > 50
- Total bilirubin must be within normal limits. Transaminases (SGOT and/or SGPT) must
be less than 2.5X the institutional upper limit of normal.
- Serum potassium within institutional limit of normal.
- Fasting blood glucose < institutional ULN.
- In the Phase I portion of this study patients may have had prior chemotherapy.
- In the Phase II portion of this study patients may not have had prior chemotherapy.
- Women of childbearing potential must have a negative pregnancy test (Phase I trial).
- Men and women of childbearing potential must consent to using effective contraception
while on treatment and for 3 months thereafter.
- Known infection with HIV. Patients without prior HIV testing will not be required to
- History of glucose intolerance.
- Patients with ongoing coagulopathies and/or receiving oral anticoagulants.
- Second primary malignancy except most situ carcinoma (e.g. in situ carcinoma of the
of the cervix, adequately treated non-melanomatous carcinoma of the skin) or other
malignancy treated at least 5 years previously with no evidence of recurrence.
- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with diabetes mellitus, hypoglycemia, history of seizure disorder, known
autonomic dysfunction, clinically significant uncontrolled gastrointestinal disorder,
known G6PD deficiency, and allergy to methylparaben or propylparaben will be
excluded, based on known potential toxicities.
- The effects of 2-deoxyglucose on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason and because Agent Class as well as
other therapeutic agents used in this trial are known to be teratogenic, 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, for the duration
of study participation and for 3 months thereafter. Should a woman become pregnant
or suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
- Active clinically significant infection requiring antibiotics.
- History of clinically significant unexplained episodes of hypotension, fainting,
dizziness, or lightheadedness.5.2.10 History or symptoms of cardiovascular disease
(NYHA Class 2, 3, or 4; see Appendix D, New York Heart Association Criteria) within
the last 6 months, particularly coronary artery disease, arrhythmias, or conduction
defects with risk of cardiovascular instability, uncontrolled hypertension,
clinically significant pericardial effusion, or congestive heart failure.
- History of transient ischemic attack, stroke, or seizure disorder or any other CNS
disease considered to be significant by the investigator.
- Major surgery within 4 weeks of the start of study treatment, without complete
- Antitumor therapy within 28 days of the start of study treatment (within 6 or 4
weeks for bicalutamide or flutamide, respectively).
- Phase I only: Inability to discontinue prohibited medications for 24 hours before and
after dosing on Cycle 1, Day 1 of Weeks 1 and 2.
- Patients who are unable (as per Investigator discretion) or unwilling to give written