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

Threshold Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Tumors

Hypoxia

Treatments

Drug: TH-302

Study type

Interventional

Funder types

Industry

Identifiers

NCT00495144

TH-CR-401

Details and patient eligibility

About

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.

Enrollment

129 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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