A study to investigate the efficacy of ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic neuroendocrine tumors of the pancreas
- Conditions
- Progressive well-differentiated metastatic pancreatic neuroendocrine tumorsMedDRA version: 21.0Level: LLTClassification code 10067518Term: Pancreatic neuroendocrine tumorSystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10068916Term: Pancreatic neuroendocrine tumor metastaticSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001207-68-DE
- Lead Sponsor
- Martin-Luther-Universität Halle-Wittenberg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 45
- 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 <1). Female patients of childbearing potential: negative serum pregnancy test within 7 days prior to first dose of protocol therapy.
- Written informed consent
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
- 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.<br>;Primary end point(s): Disease control rate (DCR) after 6 months from study entry, determined according to RECIST 1.1 or death;Timepoint(s) of evaluation of this end point: 6 months from study entry
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Objective tumor response (ORR)<br>- progression-free survival (PFS)<br>- overall survival (OS)<br>- toxicity<br>- biochemical response (tumor marker chromogranin A; in cases of functional NET: gastrin, insulin)<br>- Quality of Life (EORTC QLQ-C30 questionnaire)<br>Translational research:<br>- 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)<br>- time point of tumor progression (PFS)<br>- death of the patient (OS)<br>- Until 30 days after last administration of study therapy (toxicity)<br>- Baseline, day 1 of each cycle, end of treatment (biochemical response, predictive biomarkers)<br>