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

NCT00417287 | Terminated Phase 2 DMC

• 2 other identifiers: PX-12-II-01P01CA109552
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Pancreatic Neoplasms

Keywords

Pancreas; Cancer; Carcinoma

Outcome Measures

Primary Outcomes (2)

• Progression free survival and overall survival (percentage of patients alive at 6 months)

  6 months

• Determine if there is a difference in effect on circulating Trx-1 protein levels between two dose levels of PX-12

  21 days

Secondary Outcomes (4)

• Determine which of two dose levels of PX-12 causes the greatest effect on three surrogate markers of clinical activity

  42 days

• Determine effects of two different dose levels on overall clinical response

  42 days

• Further evaluate safety profile of PX-12

  21 days

• Assess the effects of metabolic excretion of PX-12

  3 hours

Study Arms (2)

High dose

ACTIVE COMPARATOR

128 mg/m2

Drug: PX-12

Low dose

ACTIVE COMPARATOR

54 mg/m2

Drug: PX-12

Interventions

PX-12 DRUG

3 hour intravenous infusion as a dose of either 54 mg/m2 or 128 mg/m2 daily for 5 days every three weeks.

Also known as: Thioredoxin Inhibitor

High dose; Low dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cascadian Therapeutics Inc.: lead
• National Cancer Institute (NCI): collaborator
• Translational Genomics Research Institute: collaborator

Study Sites (3)

TGen Clinical Research Services at Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

Arizona Cancer Center, University of Arizona

Tucson, Arizona, 85724, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms; Carcinoma

Interventions

thioredoxin reductase inhibitor AM12

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2006
• First Posted: January 1, 2007
• Study Start: December 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: May 16, 2018

Record last verified: 2015-04

Locations

US (3)