Clinical trial NCT00495144: A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of TH-302 in Patients With Advanced Solid Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumors
Hypoxia
Keywords: Phase I
Advanced Solid Tumors
Hypoxia
Prodrug
Multi-Center
Open-Label
Dose-Escalation
Lead sponsor: Threshold Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-07-02
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
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
Secondary outcomes:
measure: To establish the pharmacokinetics of intravenously administered TH-302
measure: To assess the anti-tumor activity of TH-302 as measured by objective response and duration of response
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TGen Drug Development Services
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: San Francisco
country: United States
facility: St. Mary's Medical Center
state: California
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers
state: Texas
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Howard Burris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Translational Drug Development
name: Glen Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References: