Solid TumorsPhase 1NCT02020226
A Cardiac Safety Study of TH-302 in Patients With Advanced Solid Tumors
A Phase 1 study testing TH-302 in people with Solid Tumors, run by Threshold Pharmaceuticals at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- TH-302
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2013to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 19Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University of Arizona Cancer Center
Tucson, Arizona, 85719
Yuma Regional Cancer Center
Yuma, Arizona, 85364
About this study
The Primary objective of this study is:
- To determine the cardiac safety of TH-302 in patients with advanced solid tumors
The Secondary objectives are:
- To assess the pharmacokinetics (PK) of TH-302
- To evaluate whether there is an association between plasma exposure to TH-302 and its active metabolite, Br-IPM, and effects on cardiac repolarization
- To assess the safety and antitumor activity of TH-302 in patients with advanced solid tumors
Read the detailed description
This is an open-label study in patients with advanced solid tumors treated with TH-302 to assess safety, pharmacokinetics, and potential effects on cardiac repolarization and antitumor activity in patients with advanced solid tumors.
A dose of 480 mg/m2 of TH 302 will be administered by IV infusion over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. Evaluations of safety, PK, and ECG parameters of cardiac repolarization will be performed on Study Day 1 and Day 2 of Cycle 1.
Cycles will be repeated every 28 days, until toxicity, progressive disease, patient or investigator decision to discontinue treatment, or until a maximum of six treatment cycles. Patients who are clearly benefitting from the treatment based on anti-cancer disease control and tolerability will be able to continue to receive drug past 6 cycles after discussion with the Sponsor. Tumor assessments will be performed after every 2 cycles during treatment.
The rationale for conducting this study is based on (a) prior data demonstrating the clinical benefit in advanced solid tumors as defined by tumor response or stable disease for at least 4 months, (b) tolerability of TH-302 at the proposed dose, and (c) a requirement to perform a dedicated ECG study to address the clinical evaluation of the potential for QT/QTc interval prolongation of TH-302.
- Conditions
- Solid Tumors
- Being tested
- TH-302
- Keywords
- TH-302, Solid Tumors, QTc, Cardiac, Evofosfamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TH-302Drug
480 mg/m2 30 min IV infusion on Days 1, 8, and 15 of a 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| TH-302 | Experimental | 480 mg/m2 by IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle Receives: Drug: TH-302 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the potential for QT/QTc interval prolongation of TH-302 in patients with solid tumors
Measured: 2 years
Secondary outcomes (2)
Evaluate association between plasma exposure to TH-302 and its active metabolite, Br-IPM, and effects on cardiac repolarization
Measured: 2 years
Safety and antitumor activity of TH-302 in patients with advanced solid tumors
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study startNov 2013
- Primary completionJul 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Threshold Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lee Cranmer, MD, PhD, Principal investigator, The University of Arizona Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02020226
- Sponsor's protocol ID
- TH-CR-414
- Status last verified
- Jun 2016
- First submitted
- 14 Nov 2013
- Last updated
- 2 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cardiac Safety Study of TH-302 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02020226
- Acronym / sponsor ID
- TH-CR-414
- Conditions
- Solid Tumors
- Keywords
- TH-302, Solid Tumors, QTc, Cardiac, Evofosfamide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Threshold PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Primary objective of this study is:
- To determine the cardiac safety of TH-302 in patients with advanced solid tumors
The Secondary objectives are:
- To assess the pharmacokinetics (PK) of TH-302
- To evaluate whether there is an association between plasma exposure to TH-302 and its active metabolite, Br-IPM, and effects on cardiac repolarization
- To assess the safety and antitumor activity of TH-302 in patients with advanced solid tumors
Detailed description
This is an open-label study in patients with advanced solid tumors treated with TH-302 to assess safety, pharmacokinetics, and potential effects on cardiac repolarization and antitumor activity in patients with advanced solid tumors.
A dose of 480 mg/m2 of TH 302 will be administered by IV infusion over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. Evaluations of safety, PK, and ECG parameters of cardiac repolarization will be performed on Study Day 1 and Day 2 of Cycle 1.
Cycles will be repeated every 28 days, until toxicity, progressive disease, patient or investigator decision to discontinue treatment, or until a maximum of six treatment cycles. Patients who are clearly benefitting from the treatment based on anti-cancer disease control and tolerability will be able to continue to receive drug past 6 cycles after discussion with the Sponsor. Tumor assessments will be performed after every 2 cycles during treatment.
The rationale for conducting this study is based on (a) prior data demonstrating the clinical benefit in advanced solid tumors as defined by tumor response or stable disease for at least 4 months, (b) tolerability of TH-302 at the proposed dose, and (c) a requirement to perform a dedicated ECG study to address the clinical evaluation of the potential for QT/QTc interval prolongation of TH-302.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TH-302 | Experimental | Drug: TH-302480 mg/m2 by IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TH-302480 mg/m2 30 min IV infusion on Days 1, 8, and 15 of a 28 day cycle | Drug | TH-302 |
Primary outcome
Evaluate the potential for QT/QTc interval prolongation of TH-302 in patients with solid tumors
Time frame: 2 years
2 secondary outcomes
Evaluate association between plasma exposure to TH-302 and its active metabolite, Br-IPM, and effects on cardiac repolarization
Time frame: 2 years
Safety and antitumor activity of TH-302 in patients with advanced solid tumors
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee Cranmer, MD, PhD principal investigator
The University of Arizona Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TH-302 in people with Solid Tumors, run by Threshold Pharmaceuticals at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the potential for QT/QTc interval prolongation of TH-302 in patients with solid tumors (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2016.