A Cardiac Safety Study of TH-302 in Patients With Advanced Solid Tumors

NCT02020226 | Unknown Phase 1

• 1 other identifier: TH-CR-414
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The Primary objective of this study is: 1\. To determine the cardiac safety of TH-302 in patients with advanced solid tumors The Secondary objectives are:

1. 1.To assess the pharmacokinetics (PK) of TH-302
2. 2.To evaluate whether there is an association between plasma exposure to TH-302 and its active metabolite, Br-IPM, and effects on cardiac repolarization
3. 3.To assess the safety and antitumor activity of TH-302 in patients with advanced solid tumors

Conditions

Solid Tumors

Keywords

TH-302; Solid Tumors; QTc; Cardiac; Evofosfamide

Outcome Measures

Primary Outcomes (1)

• Evaluate the potential for QT/QTc interval prolongation of TH-302 in patients with solid tumors

  2 years

Secondary Outcomes (2)

• Evaluate association between plasma exposure to TH-302 and its active metabolite, Br-IPM, and effects on cardiac repolarization

  2 years

• Safety and antitumor activity of TH-302 in patients with advanced solid tumors

  2 years

Study Arms (1)

TH-302

EXPERIMENTAL

480 mg/m2 by IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

Drug: TH-302

Interventions

TH-302 DRUG

480 mg/m2 30 min IV infusion on Days 1, 8, and 15 of a 28 day cycle

TH-302

Eligibility Criteria

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

You may qualify if:

• Male or Female patients at least 18 years of age
• Advanced solid tumor for which no other higher priority therapies are available
• ECOG performance status of ) to 1
• Measurable or evaluable disease by RECIST 1.1
• Refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival at least 3 months
• At least 3 weeks from previous cytotoxic chemotherapy or radiation therapy and at least 5 half-lives or 6 weeks, which ever is shorter, after targeted or biologic therapy
• Acceptable renal function defined as serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 60mL/min (by Cockcroft Gault formula)
• Acceptable liver function defined as:
• Bilirubin ≤ 1.5 x upper limit of normal (ULN); does not apply to patients with Gilbert's syndrome
• AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN); if liver metastases are present, then ≤ 5 x ULN is allowed
• Adequate bone marrow function (Absolute neutrophil count (ANC) ≥ 1,500 cells/uL; Platelets (PLT) ≥ 100,000 cells/uL)
• Adequate cardiac conduction by ECG without evidence of second- or third-degree atrioventricular block and meeting all of the following ECG criteria:
• Heart rate 45-100 beats per minute
• No evidence of second- or third-degree atrioventricular block
• QRS interval ≤ 110ms

You may not qualify if:

• History of risk factors for TdP, including family history of long QT syndrome
• Sustained systolic blood pressure (BP) \>140 mm Hg or \<90 mm Hg, diastolic BP \>100 mm Hg or \<60 mm Hg
• Uncontrolled intercurrent illness, including, but not limited to, myocardial infarction within 6 months, unstable symptomatic ischemic heart disease, active uncontrolled infection requiring systemic therapy, or psychiatric illness/social situations that would limit compliance with study requirements
• Major surgery within the 28 days preceding the first dose of study drug
• Newly diagnosed or uncontrolled cancer-related central nervous system disease
• Receiving medications that are moderate or strong inhibitors or inducers of CYP3A4 or that are sensitive substrate or substrates with a narrow therapeutic index of CYP3A4, CYP2D6, or CYP2C9 (see Appendix D)
• Unwillingness or inability to provide written informed consent and comply with the study protocol for any reason

Sponsors & Collaborators

• Threshold Pharmaceuticals: lead

Study Sites (2)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

Yuma Regional Cancer Center

Yuma, Arizona, 85364, United States

Location

Related Links

• Threshold Pharmaceuticals Company Website

MeSH Terms

Interventions

TH 302

Study Officials

• Lee Cranmer, MD, PhD

  The University of Arizona Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 14, 2013
• First Posted: December 24, 2013
• Study Start: November 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: December 1, 2016
• Last Updated: June 2, 2016

Record last verified: 2016-06

Locations

US (2)