No progression patients after first-line platinum and fluoropyrimidines based chemotherapy in HER2 negative locally advanced/metastatic gastric or gastroesophagel junction cancer MedDRA version: 21.1 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: STIVARGA - 40 MG - COMPRESSE RIVESTITE CON FILM - USO ORALE - FLACONE (HDPE) - 28 COMPRESSE
Product Name: Stivarga
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: REGORAFENIB
Sponsors
GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male of female = 18 years of age 2. Have an Eastern Cooperative Oncology Group performance status of 0 or 1 within 14 days prior to the initiation of study treatment 3. Diagnosis of histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction 4. HER2 negative gastric or gastroesophagel junction cancer ( ICH 0, IHC 1+, IHC + FISH -) 5. Locally advanced/metastatic gastric or gastroesophageal junction cancer 6. CR/PR/SD after first-line platinum compound and Fluoropyrimidines based chemotherapy 7. Measurable disease according to RECIST 1.1 criteria 8. Have adequate bone marrow function, liver function, and renal function 9. Understand, be willing to give consent, and sign the written informed consent form (ICF) prior to undergoing any studyspecific procedure. 10. If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment. 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 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s Wort) 2. Have used biologic response modifiers, such as G-CSF, within 3 weeks of study entry 3. Have had prior treatment with regorafenib or any other VEGFR-targeting kinase inhibitor. 4. Completed their last dose of chemotherapy more than 8 weeks, whichever came later, prior to randomization. 5. Have had prior or concurrent cancer distinct in primary site or histology from GC or GJC within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, no-melanoma skin cancer, or superficial bladder tumors classified as noninvasive tumor (Ta), carcinoma in situ (Tis), or tumor invades lamina propria (T1). 6. Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment. 7. Have unresolved toxicity higher than National Cancer Institute-Common Terminology for Adverse Events version 4.0 (NCI-CTCAE v 4.0) Grade 1 attributed to any prior therapy/procedure, excluding alopecia and/or oxaliplatininduced neurotoxicity = Grade 2 and hemoglobin = 9 g/dL as per inclusion criteria (see Section 0). 8. Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment. 9. Are pregnant. 10. Are breastfeeding. 11. Are unable to swallow oral tablets (crushing of study treatment tablets is not allowed). 12. Have congestive heart failure classified as New York Heart Association Class 2 or higher 13. Have had unstable angina (angina symptoms at rest) or newonset angina ¿¿3 months prior to screening. 14. Have had a myocardial infarction ¿¿6 months prior to initiation of study treatment. 15. Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin. 16. Have uncontrolled hypertension (systolic blood pressure [SBP] ¿¿140 mmHg or diastolic blood pressure [DBP] ¿¿90 mmHg) despite optimal medical management. 17. Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months prior to the initiation of study treatment. 18. Have an ongoing infection with severity of Grade 2 or above (NCI-CTCAE v 4.0). 19. Have a known history of human immunodeficiency virus infection. 20. Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy. 21. Have a seizure disorder requiring medication. 22. Have a history of organ allograft. 23. Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity. 24. Have had a hemorrhage or a bleeding event ¿¿Grade 3 (NCICTCAE v 4.0) within 4 weeks prior to the initiation of study treatment. 25. Have a nonhealing wound, ulcer, or bone fracture. 26. Have renal failure requiring hemodialysis or peritoneal dialysis. 27. Have dehydration ¿¿Grade 1 (NCI-CTCAE v 4.0). 28. Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained. 29. Have persistent proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Progression Free Survival 1 (PFS 1);Secondary Objective: -Overall Survival -Progression Free Survival 2 (PFS2) -Safety -Objective Response Rate -Quality of Live;Primary end point(s): Progression Free Survival (PFS) in all randomized patient;Timepoint(s) of evaluation of this end point: Progression Free Survival (PFS) Imaging studies will be performed at baseline, 8, 16, 24 and 32 weeks, and then every 12 weeks. The objective (confirmed) response and the progression-free survival will be assessed by RECIST criteria. Progression free survival will be calculated for all patients from the date of randomization until the date PD or death is first reported. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival Safety, Objective Response Rate, Quality of Live in all randomized patient; Progression Free Survival 2 (PFS2);Timepoint(s) of evaluation of this end point: From the start to the end date of patient's participation in the study ; PFS 2 will be calculated from the start of second line therapy to Progression or death | — |
Countries
Italy
Contacts
Public ContactServizio Informazione sulla Sperime
Pharmaceutical Development and Services srl
Outcome results
None listed