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

June 28, 2007
July 2, 2007
July 27, 2012
June 2007
December 2011   (Final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT00495144 on Archive Site
  • To establish the pharmacokinetics of intravenously administered TH-302
  • To assess the anti-tumor activity of TH-302 as measured by objective response and duration of response
Same as current
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A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of TH-302 in Patients With Advanced Solid Tumors
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
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.
Not Provided
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Tumors
  • Hypoxia
Drug: TH-302
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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June 2012
December 2011   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Threshold Pharmaceuticals
Threshold Pharmaceuticals
Not Provided
Principal Investigator: Howard Burris, MD SCRI Development Innovations, LLC
Principal Investigator: Glen Weiss, MD Translational Drug Development
Threshold Pharmaceuticals
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP