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

• Status: Unknown status
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

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. To assess the pharmacokinetics (PK) of TH-302

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. To assess the safety and antitumor activity of TH-302 in patients with advanced solid tumors

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Threshold Pharmaceuticals

Criteria

Inclusion Criteria:

• 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

• QT interval corrected for heart rate by Fridericia's formula (QTcF) ≤ 480ms

• PR interval ≤ 200ms

• No arrhythmia interpreted by the study cardiologist to be clinically significant

• Female patients of childbearing age must have a negative serum HCG test unless prior hysterectomy or menopause (defined as age ≥ 55 and twelve consecutive months without menstrual activity). Female patients should not become pregnant or breast-feed while on this study. Sexually active male and female patients should use effective birth control

Exclusion Criteria:

• Receiving QT-prolonging drugs with a risk of causing torsades de pointes (TdP), unless ECG meets inclusion criteria on a stable dose of the drug and with discussion and agreement with the project clinician

• 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