Advanced Renal Cell CarcinomaPhase 1TH-CR-410NCT01381822
Dose-Escalation Study of TH-302 in Combination With Sunitinib to Treat Patients With Advanced Renal Cell Carcinoma,Gastrointestinal Stromal Tumors and Pancreatic Neuroendocrine Tumors
A Phase 1 study testing TH-302 in people with Advanced Renal Cell Carcinoma and Gastrointestinal Stromal Tumors, run by Threshold Pharmaceuticals at 2 sites in United States.
Trial summary
The primary objectives are: Dose escalation: 1. To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib. Dose expansion: 1. To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Renal Cell Carcinoma, Gastrointestinal Stromal Tumors, Pancreatic Neuroendocrine 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
- 58 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2011to Jun 2014
- 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
- 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
- Pathologically confirmed diagnosis of
- advanced RCC or
- GIST after disease progression on or intolerance to imatinib mesylate (dose escalation only)
- Unresectable locally advanced or metastatic pancreatic neuroendocrine tumors (dose escalation only)
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- Recovered from reversible toxicities of prior therapy
- Evaluable disease by RECIST criteria (at least one target or non-target lesion for dose escalation cohorts; at least 1 target lesion for dose expansion cohort)
- ECOG performance status of 0 - 2
- Life expectancy of at least 3 months
- Acceptable liver function:
- Bilirubin less than or equal to 1.5 times upper limit of normal (ULN)
- AST (SGOT) and ALT (SGPT) less than or equal to 3.0 times ULN
- Acceptable renal function:
- Serum creatinine ≤ Upper Limit Normal,
- Acceptable hematologic status (without hematologic support):
- ANC greater than or equal to 1500 cells/μL
- Platelet count greater than or equal to 100,000/μL
- Hemoglobin great than or equal to 9.0 g/dL
- Acceptable cardiac function:
- Normal 12-lead ECG (clinically insignificant abnormalities permitted)
- LVEF normal by MUGA or echocardiogram
- Urinalysis: No clinically significant abnormalities
- Acceptable thyroid function
- All women of childbearing potential must have a negative serum pregnancy test and all 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
Who cannot join
- Prior therapy with more than 2 myelosuppressive cytotoxic chemotherapy regimens (does not include neoadjuvant and adjuvant therapy)
- Current use of drugs with known cardiotoxicity or known interactions with sunitinib (see product label)
- Anticancer treatment with radiation therapy, chemotherapy, targeted therapies (erlotinib, lapatinib, etc.), immunotherapy, hormones or other antitumor therapies within 3 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)
- Significant cardiac dysfunction:
- Cardiac events within 12 months prior to treatment including MI and severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, cerebrovascular accident or transient ischemic attack or pulmonary embolism
- > Grade 2 QTc prolongation
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- Requirement for antiarrhythmics
- Uncontrolled arrhythmias within the past 6 months
- Angina pectoris requiring antianginal medication within the past 6 months
- Clinically significant valvular heart disease
- Poorly controlled hypertension despite adequate blood pressure medication
- Seizure disorders requiring anticonvulsant therapy
- Known brain metastases (unless previously treated and well controlled for a period of greater than or equal to 3 months)
- Other active malignancy, except for adequately treated non-melanoma skin cancer, in situ cancer
- Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
- 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
- Prior therapy with an hypoxic cytotoxin
- Subjects who participated in an investigational drug or device study within 21 days prior to study entry
- Known infection with HIV or active infection with hepatitis B or hepatitis C
- Subjects who have exhibited allergic reactions to a structural compound or biological agent similar to TH-302
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
IU Health Goshen Center for Cancer Care
Goshen, Indiana, 46526
University of Iowa
Iowa City, Iowa, 52242
About this study
Official title: A Phase 1 Dose-Escalation Study to Determine the Safety of TH-302 in Combination With Sunitinib in Patients With Advanced Renal Cell Carcinoma,Gastrointestinal Stromal Tumors and Pancreatic Neuroendocrine Tumors
The primary objectives are:
Dose escalation:
Read more
- To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib.
Dose expansion:
- To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects with advanced RCC treated at the RP2D
- To assess the safety of TH-302 in combination with sunitinib and determine a recommended Phase 2 dose of the combination.
The secondary objectives are:
Dose expansion:
- To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by stable disease or better rate, duration of response and overall survival in subjects with advanced RCC treated at the RP2D.
The exploratory objective is:
- To explore the association of serum hypoxia biomarkers with efficacy endpoints.
Read the detailed description
This Phase 1 dose-escalation study will use a classic dose escalation design to determine the MTD of TH-302 when used in combination with sunitinib. The study will be divided into two parts completed in succession to determine the recommended phase 2 dose (RP2D) for dose expansion.
Part A:
The dose of TH-302 will be escalated in cohorts of 3-6 subjects. The initial dose of TH-302 will be 240 mg/m2. A Dose Level minus 1 and 2 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue with approximately 40% increases from the previous dose level; however lower dose increases of 20-39% may be implemented after consultation between the Investigators, Medical Monitor and Sponsor with the percent increase dependent on the current dose level and the cumulative safety data.
If a subject experiences a DLT, 3 additional subjects will be enrolled at that dose level for a total of 6 subjects in that cohort. If no additional DLTs are observed, dose escalation will resume. However, if 2 or more of 6 subjects within a cohort experience a DLT, that dose will be considered to exceed the MTD. The MTD will then be defined at the next lower dose level whereby 6 subjects were treated and < 1 subject experienced a DLT. The maximum dose of TH-302 will be 575 mg/m2.
The MTD will be based on toxicities occurring during the first cycle.
TH-302 will be administered by IV infusion over 30-60 minutes on Days 8, 15 and 22 of a 42-day cycle (6 weeks).
The dose of sunitinib will remain fixed: 50 mg administered PO daily on days 1 to 28 day of a 42-day cycle (6 weeks). On days when both sunitinib and TH-302 are administered, sunitinib should be administered at least 2 hours before or at least 2 hours after completion of the TH-302 dose.
Part B:
Once the MTD from Part A has been determined, Part B can commence.
The initial dose of TH-302 will be one dose level higher than the MTD established in Part A. The dose of TH-302 will be escalated in cohorts of 3-6 subjects. A Dose Level at the MTD established in Part A will be built into the study in the event that subjects experience excessive toxicity at the initial dose. Dose escalation will continue with approximately 40% increases from the previous dose level; however lower dose increases of 20-39% may be implemented after consultation between the Investigators, Medical Monitor and Sponsor with the percent increase dependent on the current dose level and the cumulative safety data.
If a subject experiences a DLT, 3 additional subjects will be enrolled at that dose level for a total of 6 subjects in that cohort. If no additional DLTs are observed, dose escalation will resume. However, if 2 or more of 6 subjects within a cohort experience a DLT, that dose will be considered to exceed the MTD. The MTD will then be defined at the next lower dose level whereby 6 subjects were treated and < 1 subject experienced a DLT.
The MTD will be based on toxicities occurring during the first cycle.
TH-302 will be administered by IV infusion over 30-60 minutes on Days 8, 15 and 22 of a 42-day cycle (6 weeks).
The dose of sunitinib will remain fixed: 37.5 mg administered PO daily on days 1 to 28 of a 42-day cycle (6 weeks).
On days when both sunitinib and TH-302 are administered, sunitinib should be administered at least 2 hours before or at least 2 hours after completion of the TH-302 dose.
An additional 10 RCC subjects will be enrolled at the recommended phase 2 dose (RP2D) for the dose expansion portion of the study.
- Conditions
- Advanced Renal Cell Carcinoma, Gastrointestinal Stromal Tumors, Pancreatic Neuroendocrine Tumors
- Being tested
- TH-302
- Keywords
- TH-302, Advanced Renal Cell Carcinoma, RCC, Gastrointestinal Stromal Tumors, GIST, Phase 1, Sunitinib, Pancreatic Neuroendocrine Tumors, PNET
- Medical subject headings
- Gastrointestinal Stromal Tumors, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TH-302Drug
TH-302: administered by IV infusion over 30 or 60 minutes on Days 8, 15 and 22 of a 42 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| TH-302 Dose escalation | Experimental | The initial dose of TH-302 will be 240 mg/m2. A Dose Level minus 1 and 2 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue with approximately 40% increases from the previous dose level; however lower dose increases of 20-39% may be implemented after consultation between the Investigators, Medical Monitor and Sponsor with the percent increase dependent on the current dose level and the cumulative safety data. Receives: Drug: TH-302 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib.
Measured: Two years
Secondary outcomes (1)
To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects with advanced RCC treated at the RP2D.
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionJun 2014 (estimated)
- Study completionJun 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Renal Cell CarcinomaStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Threshold Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alexander Starodub, MD, Principal investigator, IU Health Goshen Center for Cancer CareMohammed Milhem, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01381822
- Sponsor's protocol ID
- TH-CR-410
- Acronym
- TH-CR-410
- Status last verified
- Apr 2014
- First submitted
- 23 Jun 2011
- Last updated
- 21 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose-Escalation Study to Determine the Safety of TH-302 in Combination With Sunitinib in Patients With Advanced Renal Cell Carcinoma,Gastrointestinal Stromal Tumors and Pancreatic Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT01381822
- Acronym / sponsor ID
- TH-CR-410 / TH-CR-410
- Conditions
- Advanced Renal Cell Carcinoma, Gastrointestinal Stromal Tumors, Pancreatic Neuroendocrine Tumors
- Keywords
- TH-302, Advanced Renal Cell Carcinoma, RCC, Gastrointestinal Stromal Tumors, GIST, Phase 1, Sunitinib, Pancreatic Neuroendocrine Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Threshold PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Jun 2014 (estimated)
- First posted
- 27 Jun 2011 (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 objectives are:
Dose escalation:
- To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib.
Dose expansion:
- To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects with advanced RCC treated at the RP2D
- To assess the safety of TH-302 in combination with sunitinib and determine a recommended Phase 2 dose of the combination.
The secondary objectives are:
Dose expansion:
- To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by stable disease or better rate, duration of response and overall survival in subjects with advanced RCC treated at the RP2D.
The exploratory objective is:
- To explore the association of serum hypoxia biomarkers with efficacy endpoints.
Detailed description
This Phase 1 dose-escalation study will use a classic dose escalation design to determine the MTD of TH-302 when used in combination with sunitinib. The study will be divided into two parts completed in succession to determine the recommended phase 2 dose (RP2D) for dose expansion.
Part A:
The dose of TH-302 will be escalated in cohorts of 3-6 subjects. The initial dose of TH-302 will be 240 mg/m2. A Dose Level minus 1 and 2 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue with approximately 40% increases from the previous dose level; however lower dose increases of 20-39% may be implemented after consultation between the Investigators, Medical Monitor and Sponsor with the percent increase dependent on the current dose level and the cumulative safety data.
If a subject experiences a DLT, 3 additional subjects will be enrolled at that dose level for a total of 6 subjects in that cohort. If no additional DLTs are observed, dose escalation will resume. However, if 2 or more of 6 subjects within a cohort experience a DLT, that dose will be considered to exceed the MTD. The MTD will then be defined at the next lower dose level whereby 6 subjects were treated and < 1 subject experienced a DLT. The maximum dose of TH-302 will be 575 mg/m2.
The MTD will be based on toxicities occurring during the first cycle.
TH-302 will be administered by IV infusion over 30-60 minutes on Days 8, 15 and 22 of a 42-day cycle (6 weeks).
The dose of sunitinib will remain fixed: 50 mg administered PO daily on days 1 to 28 day of a 42-day cycle (6 weeks). On days when both sunitinib and TH-302 are administered, sunitinib should be administered at least 2 hours before or at least 2 hours after completion of the TH-302 dose.
Part B:
Once the MTD from Part A has been determined, Part B can commence.
The initial dose of TH-302 will be one dose level higher than the MTD established in Part A. The dose of TH-302 will be escalated in cohorts of 3-6 subjects. A Dose Level at the MTD established in Part A will be built into the study in the event that subjects experience excessive toxicity at the initial dose. Dose escalation will continue with approximately 40% increases from the previous dose level; however lower dose increases of 20-39% may be implemented after consultation between the Investigators, Medical Monitor and Sponsor with the percent increase dependent on the current dose level and the cumulative safety data.
If a subject experiences a DLT, 3 additional subjects will be enrolled at that dose level for a total of 6 subjects in that cohort. If no additional DLTs are observed, dose escalation will resume. However, if 2 or more of 6 subjects within a cohort experience a DLT, that dose will be considered to exceed the MTD. The MTD will then be defined at the next lower dose level whereby 6 subjects were treated and < 1 subject experienced a DLT.
The MTD will be based on toxicities occurring during the first cycle.
TH-302 will be administered by IV infusion over 30-60 minutes on Days 8, 15 and 22 of a 42-day cycle (6 weeks).
The dose of sunitinib will remain fixed: 37.5 mg administered PO daily on days 1 to 28 of a 42-day cycle (6 weeks).
On days when both sunitinib and TH-302 are administered, sunitinib should be administered at least 2 hours before or at least 2 hours after completion of the TH-302 dose.
An additional 10 RCC subjects will be enrolled at the recommended phase 2 dose (RP2D) for the dose expansion portion of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TH-302 Dose escalation | Experimental | Drug: TH-302The initial dose of TH-302 will be 240 mg/m2. A Dose Level minus 1 and 2 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue with approximately 40% increases from the previous dose level; however lower dose increases of 20-39% may be implemented after consultation between the Investigators, Medical Monitor and Sponsor with the percent increase dependent on the current dose level and the cumulative safety data. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
- Pathologically confirmed diagnosis of
- Recovered from reversible toxicities of prior therapy
- Evaluable disease by RECIST criteria (at least one target or non-target lesion for dose escalation cohorts; at least 1 target lesion for dose expansion cohort)
Key exclusion criteria (24 listed)
- Prior therapy with more than 2 myelosuppressive cytotoxic chemotherapy regimens (does not include neoadjuvant and adjuvant therapy)
- Current use of drugs with known cardiotoxicity or known interactions with sunitinib (see product label)
- Anticancer treatment with radiation therapy, chemotherapy, targeted therapies (erlotinib, lapatinib, etc.), immunotherapy, hormones or other antitumor therapies within 3 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)
- Significant cardiac dysfunction:
- Seizure disorders requiring anticonvulsant therapy
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-302TH-302: administered by IV infusion over 30 or 60 minutes on Days 8, 15 and 22 of a 42 day cycle. | Drug | TH-302 Dose escalation |
Primary outcome
To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib.
Time frame: Two years
1 secondary outcome
To make a preliminary assessment of the efficacy of TH-302 in combination with sunitinib as determined by the response rate and the progression-free survival in subjects with advanced RCC treated at the RP2D.
Time frame: Two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2014.
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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.
Alexander Starodub, MD principal investigator
IU Health Goshen Center for Cancer Care
Mohammed Milhem, MD principal investigator
University of Iowa
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 Advanced Renal Cell Carcinoma and Gastrointestinal Stromal 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 25 inclusion and 24 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 21 Apr 2014. 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?
To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib. (time frame: Two 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 21 Apr 2014; AzTrials last refreshed its copy on 6 Nov 2026.