Progressive well-differentiated metastatic pancreatic neuroendocrine tumors MedDRA version: 21.0 Level: LLT Classification code 10067518 Term: Pancreatic neuroendocrine tumor System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10068916 Term: Pancreatic neuroendocrine tumor metastatic System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Cyramza 10 mg/ml
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Martin-Luther-Universität Halle-Wittenberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically confirmed unresectable metastatic G1-G3 differentiated pancreatic neuroendocrine tumor (non-functional and functional NET) with a proliferation rate assessed by Ki-67 up to 55% - excluding neuroendocrine carcinomas - Age: 18-80 years - Measurable disease (RECIST 1.1) - Progressive disease under treatment with either non-DTIC-based chemotherapy, SSA analogues, everolimus or sunitinib. - No prior therapy with DTIC is allowed. Prior therapy with temozolomide is allowed with a temozolomide-free interval of at least 6 months prior to trial inclusion. Prior TACE and SIRT allowed with a minimum of 3 months before study entry, prior PRRT with a minimum of 12 months before study entry - ECOG 0-1 - Life expectancy > 12 weeks - Adequate renal, hepatic, bone marrow and coagulation function - Sexually active patiens: postmenopausal, surgically sterile, or use of effective contraception (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: - Pregnancy or lactation. - Secondary malignancy in patient’s history with the exception of: disease-free period > 5 years before randomization or non-melanoma skin cancer or curatively treated cervical carcinoma in situ or other noninvasive in situ neoplasm. - Allergy against dacarbazine or ramucirumab - Current enrolment or participation within the last 4 weeks in a clinical drug trial - Any arterial thromboembolic events within 6 months prior to first dose of protocol therapy. Insufficient liver function - Uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management - Chronic antiplatelet therapy, once-daily aspirin use (maximum dose 325 mg/day) permitted - Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy. - History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to first dose of protocol therapy - Uncontrolled severe physical or mental disorders - Pathological condition present that carries a high risk of bleeding - History of gastrointestinal perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation. - Major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy. Elective or planned major surgery to be performed during the course of the clinical trial. - Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy. - officially and/or legally accomodated persons
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 6 months from study entry;Main Objective: The aim of this study is to investigate whether ramucirumab in combination with dacarbacine has an effect on the disease-control in patients with progressive pancreatic neuroendocrine tumors;Secondary Objective: Secondary aims are to investigate the tumor response, survival, progression-free survival, the toxicity profile of the combination therapy, the biochemical response and Quality of Life. Additionally a translational research aims to investigate predictive biomarkers. ;Primary end point(s): Disease control rate (DCR) after 6 months from study entry, determined according to RECIST 1.1 or death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective tumor response (ORR) - progression-free survival (PFS) - overall survival (OS) - toxicity - biochemical response (tumor marker chromogranin A; in cases of functional NET: gastrin, insulin) - Quality of Life (EORTC QLQ-C30 questionnaire) Translational research: - Predictive biomarkers (circulating VEGF, ANGPT1/2 and IL8 levels, immunohistochemical VEGFR2 expression).;Timepoint(s) of evaluation of this end point: - 6 months from study entry (ORR, QoL) - time point of tumor progression (PFS) - death of the patient (OS) - Until 30 days after last administration of study therapy (toxicity) - Baseline, day 1 of each cycle, end of treatment (biochemical response, predictive biomarkers) | — |
Countries
Germany
Contacts
Public ContactPrincipal Investigator
Universitätsklinikum Halle
Outcome results
None listed