A Trial of PX-12 in Patients With a Histologically or Cytologically Confirmed Diagnosis of Advanced or Metastatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Oncothyreon Inc.
ClinicalTrials.gov Identifier:
NCT00736372
First received: August 13, 2008
Last updated: March 21, 2013
Last verified: March 2013
  Purpose

PX-12 (1-methylpropyl 2-imidazolyl disulfide) is a novel small molecule inhibitor of thioredoxin-1, a small protein over-expressed in many human cancers that is associated with aggressive tumor proliferation, angiogenesis, and drug resistance. This study is being conducted to determine the maximally tolerated dose of PX-12 delivered as a 72-hour infusion over days 1, 2, and 3 of a 21-day cycle in patients with advanced or metastatic cancer.


Condition Intervention Phase
Metastatic Cancer
Advanced Cancer
Drug: PX-12
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Oncothyreon Inc.:

Primary Outcome Measures:
  • To determine the MTD of PX-12 delivered as a 72-hour infusion over days 1, 2, and 3 of a 21-day cycle [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • When delivered as a 72 hour intravenous infusion on days 1, 2, and 3 of a 21-day cycle: Evaluate the safety profile of PX-12 [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
  • When delivered as a 72 hour intravenous infusion on days 1, 2, and 3 of a 21-day cycle: Assess the pharmacodynamics of PX-12 using surrogate tissues obtained pre- and post-drug treatment [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • When delivered as a 72 hour intravenous infusion on days 1, 2, and 3 of a 21-day cycle: Assess pharmacokinetic profiles of PX-12 in plasma samples [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • When delivered as a 72 hour intravenous infusion on days 1, 2, and 3 of a 21-day cycle: Identify any antitumor activity of PX-12 in this patient population [ Time Frame: 42 days ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: June 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Investigational Drug
Dose Escalation
Drug: PX-12
Intravenous infusion, dose escalation, infused over a 72 hour period on days 1, 2 and 3 of a 21-day cycle until progression or development of unacceptable toxicity

  Eligibility

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

Inclusion Criteria:

  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 months.
  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 > 1,500 cells/μL.

  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 follow-up.
  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

Exclusion Criteria:

  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 dyspnea.
  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 study requirements.
  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 protocol.
  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: NCT00736372

Locations
United States, Arizona
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, South Carolina
Cancer Centers of the Carolinas
Greenville, South Carolina, United States, 29605
United States, Texas
Tyler Cancer Center
Tyler, Texas, United States, 75702
Sponsors and Collaborators
Oncothyreon Inc.
  More Information

No publications provided

Responsible Party: Oncothyreon Inc.
ClinicalTrials.gov Identifier: NCT00736372     History of Changes
Other Study ID Numbers: PX-12-004
Study First Received: August 13, 2008
Last Updated: March 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Oncothyreon Inc.:
cancer
metastatic cancer
advanced or metastatic cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on September 11, 2014