Phase 1/2, Open-label, Dose-escalation Study of ISIS-STAT3Rx, Administered to Patients With Advanced Cancers

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Isis Pharmaceuticals Identifier:
First received: February 13, 2012
Last updated: November 10, 2014
Last verified: November 2014

This is a Phase 1/2, open-label, dose-escalation, dose-expansion study for the treatment of patients with advanced cancers. Eligible patients with DLBCL or other advanced lymphomas will be enrolled into the dose-expansion cohort.

Condition Intervention Phase
Advanced Cancers
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of ISIS 481464, an Antisense Oligonucleotide Inhibitor of STAT3, Administered to Patients With Advanced Cancers

Resource links provided by NLM:

Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • Safety of ISIS-STAT3Rx in patients with Advanced Cancers [ Time Frame: Approximately 28 days after last dose of ISIS -STAT3Rx ] [ Designated as safety issue: No ]
  • Maximum-tolerated dose (MTD) of ISIS-STAT3Rx in patients with Advanced Cancers. [ Time Frame: Approximately 28 Days ] [ Designated as safety issue: No ]
    Highest dose level at which no more than 1 out of 6 patients develops a DLT

Secondary Outcome Measures:
  • Clinical activity of ISIS-STAT3Rx [ Time Frame: Approximately 28 Days after last dose of ISIS-STAT3Rx ] [ Designated as safety issue: No ]
    Measured by RECIST in the study population who have measurable disease or relevant disease specific response criteria

  • Pharmacokinetics-Cmax [ Time Frame: Approximately 28 days after last dose of ISIS-STAT3Rx ] [ Designated as safety issue: No ]
    Maximum observed drug concentration (Cmax)

  • STAT3 and other biomarkers [ Time Frame: Approximately 28 days after last dose of ISIS-STAT3Rx ] [ Designated as safety issue: No ]
    The effect of treatment with ISIS-STAT3Rx on phospho-STAT3 and other biomarkers

  • Pharmacokinetics - Tmax [ Time Frame: Approximately 28 days after last dose of ISIS-STAT3Rx ] [ Designated as safety issue: No ]
    Time taken to reach Cmax

Estimated Enrollment: 80
Study Start Date: February 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Three-hour IV infusions on Cycle 0 Days 1, 3, 5, and weekly three-hour IV infusions in Cycles 1 and beyond, on Days 1, 8, and 15 of each cycle.


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

Inclusion Criteria:

  • Aged 18 years or older
  • Tumors that are relapsed or refractory to at least 1 prior anti-cancer systemic therapy and for which no standard therapy exists
  • Expansion cohort only: Advanced lymphoma confirmed by histopathology
  • Measurable or evaluable disease according to RECIST for solid tumors or according to IWRC for NHL tumors
  • ECOG Performance Status less than or equal to 2
  • Life expectancy greater than 12 weeks in the opinion of the Investigator

Exclusion Criteria:

  • Any active or uncontrolled infection
  • NYHA Grade II or greater congestive heart failure
  • History of myocardial infarction within 6 months prior to screening
  • Prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy within 4 weeks prior to screening or 5 half-lives of the therapy, whichever is shorter
  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 identifier: NCT01563302

United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
Moores UC San Diego Cancer Center
La Jolla, California, United States, 92093
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06510
United States, Georgia
Blood and Marrow Transplant Group of Georgia at Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Texas
Mary Crowley Cancer Research Centers
Dallas, Texas, United States, 75201
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Isis Pharmaceuticals
Study Director: Mason Yamashita, MD, PhD Isis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Isis Pharmaceuticals Identifier: NCT01563302     History of Changes
Other Study ID Numbers: ISIS 481464-CS1
Study First Received: February 13, 2012
Last Updated: November 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Isis Pharmaceuticals:
Advanced Cancers
Advanced Lymphoma

Additional relevant MeSH terms:
Neoplasms processed this record on October 13, 2015