Patients with well- and moderately-differentiated metastatic pancreatic neuroendocrine tumours (pNET).
Conditions
Interventions
Trade Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SUNITINIB
CAS Number: 557795-19-4
Current Sponsor code: PR-1
Sponsors
Grupo Español de Tumores Neuroendocrinos
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, 18 years of age or older. 2. ECOG performance status 0-1. 3. Histologically proven diagnosis of pancreatic neuroendocrine tumors (pNET) with Ki67 assessment of 40 mL/min (Cockroft and Gault formula) 11. Adequate cardiac function: 12-lead ECG without pathologic findings (clinically significant alterations are allowed) and Echocardiogram / Normal MUGA (LVEF> 50%) 12. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 43 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: 1. Previous treatments with chemotherapy, monoclonal antibodies anti-VEGF, tyrosine kinase inhibitors, mTOR inhibitors, or interferon are not permitted for the advanced disease. 2. Prior treatment on another hypoxia-activated prodrug under clinical trial. 3. Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization except palliative radiotherapy to non-target metastatic lesions. 4. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 5. Immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken concurrently or within last 3 months prior to randomization 6. Treatment with known inhibitors or inductors of CYP3A4 or that prolong the QT interval in the previous 7 days. 7. Prior radiation therapy to >25% of the bone marrow. 8. Current treatment on another clinical trial. 9. Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients should have completed surgery or radiation therapy for existing brain metastases, should not have documented increase in size over the previous 3 months prior to first dose of treatment on study and should be asymptomatic. 10. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. 11. Any of the following within the 12 months prior to starting study treatment: - myocardial infarction, - severe/unstable angina, - coronary/peripheral artery bypass graft, - congestive heart failure class III or IV of the New York Heart Association (NYHA) or patients with clinical history of congestive heart failure clase III or IV of the NYHA, unless an echocardiogram or MUGA in the pevious 3 months to selection shows a LVEF ? 45 % - significant heart valve disease - cerebrovascular accident including transient ischemic attack - pulmonary embolus. 12. Ongoing cardiac dysrhythmias of NCI CTCAE grade ? 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. 13. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy) 14. Chronic obstructive pulmonary disease (COPD) or any other disease concurrent with hypoxemia or oxigen saturation < 90% after a march of two minutes. 15. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 16. Known human immunodeficiency virus infection. 17. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to inclusion. 18. Previous allergic reaction to components structurally similar to TH-302 or sunitinib or any of the excipients of drugs. 19. Non-healing wound, fistulae, active peptic ulcer or bone fracture. 20. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, ex
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Objective Response Rate (OOR); Secondary Objective: Progression Free Survival (PFS) Time to Tumour Progression (TTP) Duration of Response (DR) Overall Survival (OR) Safety Biomarkers in serum and tumor tissue ;Primary end point(s): Objective response rate: percentage of patients in whom a complete response (CR) or a partial response (PR) is confirmed according RECIST criteria in relation to the total of the analysed population.;Timepoint(s) of evaluation of this end point: the objective response rate will be assessed according to RECIST criteria which will be held every 8 weeks, regardless of delays in the secondary treatment toxicity. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression Free Survival (PFS) - Time between the start of study treatment to date of the first objective evidence of radiological progression or patient death due to any cause; which comes first. Time to Tumour Progression (TTP) - It is defined as the time between the start of study treatment to date of the first objective evidence of radiological progression. Duration of Response (DR) - It is defined as the time between the start from the first documentation of objective response (CR or PR) which is subsequently confirmed until the first objective evidence of radiological progression or death from any cause. DR is calculated only in the subgroup of patients with an objective response (CR + PR). Overall Survival (OR) - It is defined as the time between the start of study treatment to date of death from any cause. If it were impossible to obtain confirmation of the death, survival will be censored with the date of the last visit that it is satisfied that the patient was alive. Safety - The safety period includes the time between the date of signing the informed consent until 28 days after the last dose of study drug. Safety will be assessed according to the reports of adverse events, the frequency of treatment discontinuations due to adverse events, laboratory evaluations or ECG Biomarkers in serum and tumor tissue ? See sub-study ; Timepoint(s) of evaluation of this end point: Progression Free Survival (PFS) - duration of the trial Time to Tumour Progression (TTP) - duration of the trial Duration of Response (DR) - duration of the trial Overall Survival (OR) - duration of the trial Safety - The safety period includes the time between the date of signing the informed consent until 28 days after the last dose of study drug Biomarkers in serum | — |
Countries
Spain
Contacts
Public ContactFederico Nepote
MFAR, S.L.
Outcome results
None listed