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

NCT00495144 | Completed Phase 1 DMC

• 1 other identifier: TH-CR-401
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 7

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.

Conditions

Tumors; Hypoxia

Keywords

Phase I; Advanced Solid Tumors; Hypoxia; Prodrug; Multi-Center; Open-Label; Dose-Escalation

Outcome Measures

Primary Outcomes (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 Outcomes (2)

• 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

Interventions

TH-302 DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Threshold Pharmaceuticals: lead

Study Sites (7)

TGen Drug Development Services

Scottsdale, Arizona, 85258, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

St. Mary's Medical Center

San Francisco, California, 94117, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75201, United States

Location

Related Links

• Threshold Pharmaceuticals Company Website

MeSH Terms

Conditions

Neoplasms; Hypoxia

Interventions

TH 302

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Howard Burris, MD

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

• Glen Weiss, MD

  Translational Drug Development

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2007
• First Posted: July 2, 2007
• Study Start: June 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2012
• Last Updated: July 27, 2012

Record last verified: 2012-07

Locations

US (7)