Advanced pancreatic adenocarcinoma MedDRA version: 21.0 Level: LLT Classification code 10033599 Term: Pancreatic adenocarcinoma metastatic System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Cyramza 10 mg/ml concentrate for solution for infusion
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RAMUCIRUMAB
CAS Number: 947687-13-0
Other descriptiv
Sponsors
Hellenic Cooperative Oncology Group (HeCOG)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent and willing and able to comply with protocol requirements. 2. Histologically or cytologically proven pancreatic adenocarcinoma. 3. Metastatic or locally advanced unresectable disease confirmed clinically/radiologically by CT-scan or MRI (Magnetic Resonance Imaging) 4. No prior therapy for metastatic disease. Adjuvant Gemcitabine is permitted if 6 or more months have elapsed from last cycle to date of relapse. 5. At least one measurable or evaluable lesion as assessed by CT-scan or MRI according to RECIST v1.1 6. Age 18 years, 7. ECOG Performance status (PS) 0-1 8. The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) 1500/µL, hemoglobin 9 g/dL (5.58 mmol/L), and platelets 100,000/µL. 9. The patient must have adequate coagulation function as defined by International Normalized Ratio (INR) 1.5, and a partial thromboplastin time (PTT) 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy 10. The patient has adequate renal function as defined by a serum creatinine 1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) 40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed). 11. The patient has adequate hepatic function as defined by a total bilirubin 1.5 mg/dL (25.65 µmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) 2.5 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases) 12. The patient’s urinary protein is 1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is 2+, a 24-hour urine collection for protein must demonstrate <1000 mg of protein in 24 hours to allow participation in this protocol). 13. Regular follow-up feasible 14. Baseline evaluations performed before treatment initiation: clinical and blood evaluations no more than 2 weeks (14 days) prior to treatment initiation, tumor assessment (chest X ray, CT-scan or MRI, evaluation of non-measurable lesions) no more than 4 weeks (28 days) prior to treatment initiation, 15. First course of treatment planned less than 1 week (7 days) after registration, 16. Because the teratogenicity of ramucirumab is not known, the patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). 17. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy. 18. Female patients must commit to using reliable and appropriate methods of contraception during the trial until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another reliable contraceptive method during the trial until at least 6 months after the end of study treatment. 19. Patients must have a low or intermediate risk of arterial or venous thrombotic events (Khorana risk score 0-2). Patients at a high VTE risk (Khorana RS3) are eligible if they receive LMWH prophylaxis (Appendix D). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64
Exclusion criteria
Exclusion criteria: 1.The patient has pancreatic cancer with histology other than adenocarcinoma 2.Prior therapy for metastatic disease. Adjuvant Gemcitabine is permitted if 6 or more months have elapsed from last cycle to date of relapse. 3.Exclusive presence of bone metastasis only 4.Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy) 5.Treatment with any other investigational medicinal product within 28 days prior to study entry 6.Other serious and uncontrolled non-malignant chronic disease 7.The patient has: - cirrhosis at a level of Child-Pugh B (or worse) or- cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. - Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis. 8.The patient has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression. Screening of asymptomatic patients is not required. 9.Treatment with CYP3A4 or CYP2C8 inducers or inhibitors, unless discontinued > 7 days prior to prior to first dose of protocol therapy 10. The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325mg/day) is permitted. 11.The patient has experienced grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis within 3 months prior to first dose of protocol therapy. 12.Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years 13.Any other serious and uncontrolled non-malignant disease within the last 28 days 14.Pregnant or breastfeeding women 15.Patients with known allergy to any excipients to study drugs 16.The patient has symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia 17.Bowel obstruction 18.The patient has a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation. 19.The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy. 20.The patient has undergone 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. 21.The patient has elective or planned major surgery to be performed during the course of the clinical trial. 22.History of severe tumor bleeding or bleeding disorders. The patient has experienced any Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy. 23.Inadequate coagulation function as defined by International Normalized Ratio (INR) > 1.5, and a partial thromboplastin time (PTT) >5 seconds above the ULN (unless receiving anticoagulation therapy- only low molecular weight heparin injections permitted). 24.Palliative radiation therapy within 4 weeks prior to registration 25.The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient isch
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Phase Ib: The safety of the combination of Nab-paclitaxel - Gemcitabine with Ramucirumab in 4-weekly cycles by determining the Recommended Dose (RD) during the first two cycles of therapy (8 weeks). - Phase II: Efficacy by determination of the objective response rate (ORR) by RECIST criteria of the combination of Ramucirumab with Nab-paclitaxel and Gemcitabine administered in 4-weekly cycles;Secondary Objective: - To evaluate the efficacy of the combination of Ramucirumab with Nab-paclitaxel and Gemcitabine in terms of overall survival (OS) and progression-free survival (PFS). - To evaluate the safety of the combination of Ramucirumab with Nab-paclitaxel and Gemcitabine. Phases Ib and II will be analyzed separately for safety. - To investigate potential biomarkers for benefit from Ramucirumab with Nab-paclitaxel and Gemcitabine in the context of translational research.;Primary end point(s): - Phase Ib: to examine the safety by identifying the Recommended Dose (RD) of the combination of Ramucirumab with Nabpaclitaxel and Gemcitabine. - Phase II: Overall Response Rate is defined as the proportion of patients with confirmed Complete Response or confirmed Partial Response as best overall response to treatment, based on RECIST v. 1.1 guidelines in the considered analysis population.;Timepoint(s) of evaluation of this end point: - Phase Ib: From the time the patient is enrolled, in every cycle and up to 30 days after the last administration of any investigational product. - Phase II:Tumor assessment will be performed every 8 weeks until month 8 and then every 12 weeks or sooner if deemed necessary until the end of study as determined at section. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Overall survival -Progression-free survival -the safety of the combination of Nabpaclitaxel Gemcitabine with Ramucirumab treatment: a. Phase I:Toxicity profile of the combination during the first 2 cycles of therapy, b. Phase II: Adverse events and serious adverse events. Adverse Events (AEs) will be graded according to NCI-CTCAE v4.0 - Potential biomarkers to be studied include SPARC, PIK3CA, PTEN, MEK, AREG, EREG, VEGF-A, VEGF-B, PlGF, TSP1, MMP2, MMP9, VEGFR1-3 gene mutation, mRNA and protein expression. ;Timepoint(s) of evaluation of this end point: -Tumor assessment will be performed every 8 weeks until month 8 and then every 12 weeks or sooner if deemed necessary until the end of study as determined at section. -Tumor assessment will be performed every 8 weeks until month 8 and then every 12 weeks or sooner if deemed necessary until the end of study as determined at section. -In every cycle. - At baseline, in cycles 1 and 3, at maintenance therapy and at disease progression. | — |
Countries
Greece
Contacts
Public ContactClinical Trials
Hellenic Cooperative Oncology Group (HeCOG)
Outcome results
None listed