A Phase Ib Trial of PX-12 Administered as a 72-Hour Infusion Every 21 Days in Patients With a Histologically or Cytologically Confirmed Diagnosis of Advanced or Metastatic Cancer That is Refractory to Standard Treatment
1. Patients with histologically or cytologically confirmed diagnosis of advanced or
metastatic cancer or lymphoma whose tumors are refractory to standard therapy or for
whom no standard therapy is available that increases survival by at least three
2. Men and women at least 18 years of age.
3. A predicted life expectancy of at least 12 weeks.
4. ECOG performance status of 0-2 .
5. Patients must have discontinued previous anticancer therapy and/or other
investigational agents at least three weeks prior to treatment with PX-12 (six weeks
for mitomycin C and nitrosureas) and recovered (grade 1 or less) from the toxic
effects of that treatment. In the case of oral agents with a short half life, on a
case by case basis, a minimum of a two week interval may be permitted.
6. Patients must have discontinued any radiation therapy at least four weeks prior to
treatment with PX-12 and have recovered from all radiation-related toxicities.
Palliative radiation of 10 fractions or less is permitted and a four week interval is
not necessary (also allowed during therapy).
7. The patient has adequate hematologic function as defined by the following:
platelets >100,000/μL; hemoglobin >9 g/dL (may be transfused to this level); ANC >
8. The patient has adequate hepatic function as defined by the following: bilirubin <2.0
mg/dL;aspartate aminotransaminase (AST/SGOT) & alanine aminotransferase (ALT/SGPT)
<2.5 times (or up to five ULN for patients with liver metastases) institutional upper
limit of normal (ULN). International Normalized Ratio (INR) and activated partial
thromboplastin time (aPTT) within 1.5 times ULN unless subject is on coumadin.
9. The patient has adequate renal function as defined by serum creatinine level
≤ 1.5 x ULN.
10. Patient has signed informed consent.
11. Patient is compliant with the study and in geographic proximity to allow adequate
12. 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. Childbearing potential will be defined as women who have had menses
within the past 12 months, who have not had tubal ligation or bilateral oophorectomy.
Should a woman become pregnant or suspect that she is pregnant while participating in
this study, she should inform her treating physician
1. Patients with symptomatic pulmonary disease, e.g., active chronic
obstructive/restrictive pulmonary disease, asthma, evidence of interstitial
pneumonitis, pulmonary fibrosis, etc.
2. Patients with history of dyspnea, dyspnea on exertion, or paroxysmal nocturnal
3. Patients that meet the Medicare criteria for receiving home oxygen or are on oxygen.
4. Patients with a history of prior lung radiation.
5. Patients with any active infection requiring i.v. antibiotics at study entry.
6. Any serious concomitant systemic disorders that in the opinion of the investigator
would place the patient at excessive or unacceptable risk of toxicity.
7. Significant central nervous system or psychiatric disorder(s) that preclude the
ability of the patient to provide informed consent.
8. 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.
9. Major surgery within four weeks of treatment with PX-12.
10. Patients with a history of seizures.
11. 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
12. Patients who are breastfeeding or pregnant (confirmed by serum β-HCG within 10 days
prior to the start of study treatment if applicable).
13. Any condition that could jeopardize the safety of the patient and compliance with the