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

• Register: ClinicalTrials.gov
• Last refreshed on: 18 March 2013
• Main ID: NCT01381822
• Date of registration: 23/06/2011
• Primary sponsor: Threshold Pharmaceuticals
• Public title: 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 TH-CR-410
• Scientific 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
• Date of first enrolment: June 2011
• Target sample size: 58
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01381822
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Esther Chu

• Name: Alexander Starodub, MD
• Affiliation: IU Health Goshen Center for Cancer Care

• Name: Mohammed Milhem, MD
• Affiliation: University of Iowa

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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)

- 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

Exclusion Criteria:

- 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

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Advanced Renal Cell Carcinoma

Gastrointestinal Stromal Tumors

Pancreatic Neuroendocrine Tumors

Intervention(s)

Drug: TH-302

Primary Outcome(s)

To determine the MTD and DLT(s) of TH-302 when used in combination with sunitinib. [Time Frame: Two years]

Secondary Outcome(s)

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]

Secondary ID(s)

TH-CR-410

Source(s) of Monetary Support

Please refer to primary and secondary sponsors