A Randomized Phase II Open-Label Study of Two Different Dose Levels of PX-12 in Patients With Advanced Carcinoma of the Pancreas Whose Tumors Have Progressed on Gemcitabine or on a Gemcitabine-Containing Combination
- Histologically- or cytologically-confirmed diagnosis of advanced carcinoma of the
pancreas (stage IV disease only).
- Patients whose tumor has progressed on gemcitabine or on a gemcitabine-containing
combination. Patients must have received no more than two prior regimens for
metastatic disease. Use of gemcitabine as a radiation sensitizer in combination with
radiotherapy for localized disease will not be considered a prior
gemcitabine-containing regimen if gemcitabine was received for ≤ 1 month following
completion of radiotherapy. In addition, the use of 5-fluorouracil as a radiation
sensitizer for localized disease will be allowed and not counted as a prior regimen
if the 5-FU was continued for ≤ 1month following completion of radiotherapy.
- Karnofsky Performance Status of ≥ 70%.
- Patients must have discontinued previous anti-cancer therapy or other investigational
agent at least three weeks or within 5 half lives of the drug (whichever is shorter)
prior to entry into the study (six weeks for mitomycin C or nitrosureas) provided
that all toxicities from prior treatment have resolved to a Grade 1 or less.
- Patients must have discontinued radiation therapy at least two weeks prior to entry
into the study and have recovered from all radiation-related toxicities.
- Adequate organ function including the following:
- ANC ≥ 1500 cells/microL; platelets > 100,000/microL; hemoglobin ≥ 9 g/dL (may be
transfused to this level).
- Bilirubin ≤ 2.0 mg/dL; aspartate transaminase (AST/SGOT) and alanine transaminase
(ALT/SGPT) ≤ 3.0 times institutional upper limit of normal (ULN) OR < 5 times
institutional ULN if the subject has documented liver metastases.
- Creatinine ≤2.0 mg/dL.
- CA19-9 level >2 times ULN.
- Disease that is measurable by CT scan per RECIST criteria (Appendix IV).
- PET/CT or PET scan with SUV of ≥ 5.0 in at least one lesion on an 18F FDG scan.
- Active infection requiring antibiotics at study entry.
- Any serious concomitant systemic disorder that in the opinion of the investigator
would place the patient at excessive or unacceptable risk of toxicity.
- Patients with active (requiring continuous medical therapy) pulmonary disease (COPD,
asthma) or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline
chest X-ray or PET/CT scan.
- Significant central nervous system 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.
Patients must be stable without requirement for steroids or seizure medications.
- Major surgery within 4 weeks of study entry.
- Chemotherapy/investigational drugs within 3 weeks or within 5 half lives of the drug
(whichever is shorter) of study entry, provided that all toxicities from prior
treatment have resolved to a Grade 1 or less.
- Inability to tolerate prophylactic (1 mg/day) coumadin.