A Phase 1 Trial of Oral PX-478 (a HIF-1α Inhibitor) in Patients With Advanced Solid Tumors or Lymphoma
- The patient has signed the informed consent and must be considered legally capable of
providing his or her own consent for participation in this study.
- The patient has a histologically or cytologically confirmed diagnosis of advanced
solid tumor or lymphoma and has failed or is intolerant of standard therapy.
- The patient is ≥18 years of age.
- ECOG performance status 0 to 1.
- The patient has a predicted life expectancy of at least 12 weeks.
- Patients must have discontinued prior chemotherapy or other investigational agents
for at least three weeks prior to receiving the first dose of study drug (six weeks
for mitomycin C, nitrosureas, vaccines, or antibody therapy) and recovered from the
toxic effects of that treatment (recovered to baseline or ≤Common Toxicity Criteria
for Adverse Events (CTCAE) grade 1).
- Patients must have discontinued any radiation therapy at least four weeks prior to
entry into the study and have recovered from all radiation-related toxicities
(recovered to baseline or ≤CTCAE grade 1).
- The patient has adequate hematologic function defined as: WBC count >3,000 cells/μL;
platelets >100,000/μL; hemoglobin >9 g/dL (may be transfused to this level); ANC
- The patient has adequate hepatic function defined as: bilirubin <1.5 mg/dL; aspartate
aminotransaminase (AST/SGOT) & alanine aminotransferase (ALT/SGPT) <2.5 x ULN or <5 x
ULN if due to metastatic disease.
- The patient has adequate renal function as defined by serum creatinine level <1.5
- Women of childbearing potential must agree to use adequate contraception (hormonal or
barrier method; abstinence) prior to study entry and for the duration of study
participation. The patient, if a man, agrees to use effective contraception or
- Patients with any active infection requiring i.v. antibiotics at study entry.
- Any serious concomitant systemic disorders that in the opinion of the investigator
would place the patient at excessive or unacceptable risk of toxicity.
- Surgery within the four weeks prior to the first dose of PX 478.
- Significant central nervous system (CNS) or psychiatric disorder(s) that preclude the
ability of the patient to provide informed consent.
- Known or suspected brain metastases that have not received adequate therapy. In the
case of previously treated brain metastases, a minimum of four weeks interval between
completion of radiation therapy and registration on study with radiologic evidence of
stable or responding brain metastases is required. In the setting of previous CNS
metastasectomy, adequate (minimum four week) recovery from surgery and/or radiation
therapy should be documented.
- Patients with a history of seizures, non-healing wounds, or arterial thrombosis.
- Patients with unstable atrial or ventricular arrhythmias requiring control by
medication; any cardiac ischemic event experienced within the preceding six months;
prior history of congestive heart failure requiring therapy.
- Patients who are breastfeeding or pregnant (confirmed by serum β-HCG within 10 days
prior to the start of study treatment if applicable).
- Patients with total gastrectomy or partial bowel obstruction.
- Any condition that could jeopardize the safety of the patient and compliance with the