A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of TH-302 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00495144
Recruitment Status : Completed
First Posted : July 2, 2007
Last Update Posted : July 27, 2012
Information provided by (Responsible Party):
Threshold Pharmaceuticals

Brief Summary:
This is a phase I, multi-center, open-label, dose-escalation study of TH-302 in patients with advanced solid tumors. TH-302 is a hypoxia activated product designed to exploit the hypoxic nature of tumors. The study is designed to establish the safety including the maximum tolerated dose, the pharmacokinetics, and the anti-tumor activity of TH-302.

Condition or disease Intervention/treatment Phase
Tumors Hypoxia Drug: TH-302 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Multi-Center, Open-Label, Dose-Escalation Study of the Safety, Pharmacokinetics and Anti-Tumor Activity of TH-302 in Patients With Advanced Solid Tumors
Study Start Date : June 2007
Actual Primary Completion Date : December 2011
Actual Study Completion Date : June 2012

Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of TH-302 administered weekly x 3, repeated every 4 weeks in patients with advanced solid tumors

Secondary Outcome Measures :
  1. To establish the pharmacokinetics of intravenously administered TH-302
  2. To assess the anti-tumor activity of TH-302 as measured by objective response and duration of response

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • At least 18 years of age
  • Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
  • Histologically or cytologically confirmed advanced or metastatic solid malignancy
  • Advanced or metastatic solid malignancy previously treated with one or more regimens of chemotherapy or for which no effective therapy is available
  • Recovered from toxicities of prior therapy
  • Measurable disease by RECIST criteria (at least one target lesion)
  • ECOG performance status of 0 or 1
  • Life expectancy of at least 3 months
  • Acceptable liver function:

    • Bilirubin ≤ 1.5 times upper limit of normal
    • AST (SGOT) and ALT (SGPT) ≤ 2.5 times upper limit of normal (ULN); if liver metastases are present, then ≤ 5 x ULN is allowed
  • Acceptable renal function:

    • Serum creatinine ≤ ULN
  • Acceptable hematologic status (without hematologic support):

    • ANC ≥ 1500 cells/μL
    • Platelet count ≥ 100,000/μL
    • Hemoglobin ≥ 9.0 g/dL
  • Urinalysis: No clinically significant abnormalities
  • Acceptable coagulation status:

    • PT ≤ 1.3 x ULN
    • PTT ≤ 1.3 x ULN
  • All women of childbearing potential must have a negative serum pregnancy test and women and men subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose

Exclusion Criteria:

  • Prior treatment with high dose chemotherapy
  • Prior radiotherapy to more than 25% of the bone marrow
  • New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, or unstable arrhythmia
  • Seizure disorders requiring anticonvulsant therapy
  • Symptomatic brain metastases (unless previously treated and well controlled for a period of ≥ 3 months)
  • Severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state leading to hypoxemia
  • Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Treatment with radiation therapy, surgery, chemotherapy, targeted therapies (erlotinib, lapatinib, etc.) or hormones within 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C)
  • Patients who participated in an investigational drug or device study within 28 days prior to study entry
  • Known infection with HIV, hepatitis B, or hepatitis C
  • Patients who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation (containing solutol and/or propylene glycol)
  • Females who are pregnant or breast-feeding
  • Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
  • Unwillingness or inability to comply with the study protocol for any reason

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00495144

United States, Arizona
TGen Drug Development Services
Scottsdale, Arizona, United States, 85258
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
St. Mary's Medical Center
San Francisco, California, United States, 94117
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Research Centers
Dallas, Texas, United States, 75201
Sponsors and Collaborators
Threshold Pharmaceuticals
Principal Investigator: Howard Burris, MD SCRI Development Innovations, LLC
Principal Investigator: Glen Weiss, MD Translational Drug Development

Responsible Party: Threshold Pharmaceuticals Identifier: NCT00495144     History of Changes
Other Study ID Numbers: TH-CR-401
First Posted: July 2, 2007    Key Record Dates
Last Update Posted: July 27, 2012
Last Verified: July 2012

Keywords provided by Threshold Pharmaceuticals:
Phase I
Advanced Solid Tumors

Additional relevant MeSH terms:
Signs and Symptoms, Respiratory
Signs and Symptoms