A multicenter single-arm pilot study of ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic pancreatic neuroendocrine tumors
- Conditions
- Malignant neoplasm of pancreasMedDRA - 10067518MedDRA - 10068916C25
- Registration Number
- DRKS00014689
- Lead Sponsor
- Martin-Luther-Universität Halle-WittenbergMedizinische Fakultät
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- 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 C 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
- 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.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Disease-control rate (DCR) at 6 months according to RECIST 1.1
- Secondary Outcome Measures
Name Time Method - Objective tumor response (ORR, descriptively until end of study)<br>- progression-free survival (PFS, descriptively until end of study)<br>- overall survival (OS, descriptively until end of study)<br>- toxicity (descriptively until 30 days after end of treatment)<br>- biochemical response represented by tumor marker chromogranin A; in cases of functional NET: gastrin, insulin (before start of therapy, after 3 & 6 months during therapy and at end of treatment)<br>- Quality of Life (EORTC QLQ-C30 questionnaire, every 3 months until end of treatrment)