A Phase II Study to Assess the Activity and Safety of TH-302 in Combination With Sunitinib in Treatment-naïve Patients With Well- and Moderately-differentiated Metastatic Pancreatic Neuroendocrine Tumours (pNET)

Grupo Espanol de Tumores Neuroendocrinos10 sites in 1 country17 target enrollmentMay 11, 2015

ConditionsNeuroendocrine Tumors Pancreatic Neoplasms

InterventionsTH-302 + Sunitinib

DrugsTH-302 + Sunitinib

Overview

Phase: Phase 2
Intervention: TH-302 + Sunitinib
Conditions: Neuroendocrine Tumors
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Enrollment: 17
Locations: 10
Primary Endpoint: Objective Response Rate
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the safety and the efficacy of the combination of the drugs TH-302 and sunitinib in metastatic neuroendocrine tumours.

Detailed Description

The purpose of this study is to determine the safety and the efficacy of the combination of the drugs TH-302 and sunitinib in Treatment-naïve patients with well- and moderately-differentiated metastatic Pancreatic Neuroendocrine Tumours (pNET).

Registry

clinicaltrials.gov

Start Date

May 11, 2015

End Date

January 10, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Grupo Espanol de Tumores Neuroendocrinos

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female, 18 years of age or older.
•Eastern Cooperative Oncology Group (ECOG) performance status 0-
•Histologically proven diagnosis of pancreatic neuroendocrine tumors (pNET) with Ki67 assessment of ≤ 20% (well and moderately differentiated)
•Evidence of unresectable disease or metastatic disease. Locally advanced disease must not be amendable to resection or radiation therapy with curative intent.
•Patients may be treated with somatostatin analogues prior or during the trial. Concomitant or prior interferon treatment is not permitted.
•Documented progression disease by CT scan, magnetic resonance (MR) or Octreoscan in 12 months prior basal visit.
•Measurable disease as per RECIST. Measurable lesions that have been previously radiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy.
•Patient has to be able to swallow the medication.
•Life expectancy greater than 12 weeks.
•The definitions of minimum adequacy for organ function required prior to study entry are as follows:

Exclusion Criteria

•Previous treatments with chemotherapy, monoclonal antibodies anti-vascular endothelial growth factor (VEGF), tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, or interferon are not permitted for the advanced disease.
•Prior treatment on another hypoxia-activated prodrug under clinical trial.
•Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization except palliative radiotherapy to non-target metastatic lesions.
•Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
•Immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken concurrently or within last 3 months prior to randomization
•Treatment with known inhibitors or inductors of cytochrome P450 3A4 (CYP3A4) or that prolong the QT interval in the previous 7 days.
•Prior radiation therapy to \> 25% of the bone marrow.
•Current treatment on another clinical trial.
•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.
•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.

Arms & Interventions

TH-302 + Sunitinib

TH-302 + Sunitinib. Single arm Study.

Intervention: TH-302 + Sunitinib

Outcomes

Primary Outcomes

Objective Response Rate

Time Frame: approximately 36 months

Objective response rate: percentage of patients in whom a complete response (CR) or a partial response (PR) is confirmed according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in relation to the total of the analyzed population. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions

Secondary Outcomes

Progression Free Survival (PFS)(approximately 36 months)
Time to Tumour Progression (TTP)(approximately 36 months)
Duration of Response (DR)(approximately 36 months)
Overall Survival (OR)(approximately 36 months)
Safety (Adverse Events)(time between the date of signing the informed consent until 28 days after the last dose of study drug, , an average of 2 years)
Biomarkers in Serum and Tumor Tissue(approximately 36 months)