Phase II Study of PX-12 in Patients With Advanced Pancreatic Cancer

This study has been terminated.
(Investigator decision)
Sponsor:
Collaborators:
Translational Genomics Research Institute, Phoenix, Arizona.
Information provided by (Responsible Party):
Oncothyreon Inc.
ClinicalTrials.gov Identifier:
NCT00417287
First received: December 29, 2006
Last updated: March 21, 2013
Last verified: March 2013
  Purpose

This study is being conducted to evaluate the clinical efficacy, biologic activity (inhibition of PX-12 target thioredoxin-1) and effects of an expired metabolite of PX-12 in patients with advanced pancreatic cancer.


Condition Intervention Phase
Pancreatic Neoplasms
Drug: PX-12
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Oncothyreon Inc.:

Primary Outcome Measures:
  • Progression free survival and overall survival (percentage of patients alive at 6 months) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Determine if there is a difference in effect on circulating Trx-1 protein levels between two dose levels of PX-12 [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine which of two dose levels of PX-12 causes the greatest effect on three surrogate markers of clinical activity [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Determine effects of two different dose levels on overall clinical response [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Further evaluate safety profile of PX-12 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Assess the effects of metabolic excretion of PX-12 [ Time Frame: 3 hours ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: December 2006
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: High dose
128 mg/m2
Drug: PX-12
3 hour intravenous infusion as a dose of either 54 mg/m2 or 128 mg/m2 daily for 5 days every three weeks.
Other Name: Thioredoxin Inhibitor
Active Comparator: Low dose
54 mg/m2
Drug: PX-12
3 hour intravenous infusion as a dose of either 54 mg/m2 or 128 mg/m2 daily for 5 days every three weeks.
Other Name: Thioredoxin Inhibitor

Detailed Description:

In a Phase I trial, PX-12 demonstrated anti-tumor activity and pharmacodynamic activity across a wide dose range. At higher doses, one side effect of the agent was a garlic-like odor of an expired metabolite. This study is being conducted to evaluate the clinical efficacy, biologic activity (inhibition of PX-12 target thioredoxin-1) and effects of the expired metabolite at two dose levels of PX-12. This study will determine if the efficacy and biologic activity achieved at either of the two dose levels is sufficient to proceed to further studies without pushing to the maximally tolerated dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00417287

Locations
United States, Arizona
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
Arizona Cancer Center, University of Arizona
Tucson, Arizona, United States, 85724
United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Oncothyreon Inc.
Translational Genomics Research Institute, Phoenix, Arizona.
  More Information

No publications provided

Responsible Party: Oncothyreon Inc.
ClinicalTrials.gov Identifier: NCT00417287     History of Changes
Other Study ID Numbers: PX-12-II-01, P01 CA109552
Study First Received: December 29, 2006
Last Updated: March 21, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Oncothyreon Inc.:
Pancreas
Cancer
Carcinoma

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 22, 2014