Entry Detail
| General information | |
| Database: | DB00662 |
| Objective: | This prospective, openlabelphase II clinical trial was designed to determine if mutationtargeting therapy with sunitinib or everolimus for patients with advanced lowgrade or intermediategrade NETs is more effective than historically expected results with progression free survival (PFS) as the primary end point. |
| Authors: | Neychev V, et al |
| Title: | Mutationtargeted therapy with sunitinib or everolimus in patients with advanced lowgrade or intermediategrade neuroendocrine tumours of the gastrointestinal tract and pancreas with or without cytoreductive surgery: protocol for a phase II clinical trial. |
| Journal: | BMJ Open. |
| Year: | 2015 |
| PMID: | 25991462 |
| Trial Design | |
| Clinical Trial Id: | NCT02315625 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | neuroendocrine tumour |
| Cancer Subtype: | advanced lowgrade or intermediategrade neuroendocrine tumours of thegastrointestinal tract and pancreas |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a prospective, openlabelphase II clinical trial |
| Key Patients Feature: | Progressive, histologically or cytologically diagnosedlowgrade or intermediategrade, neuroendocrine tumours confirmed by the Laboratory of Pathology, National Cancer Institute (NCI). Age more than and equal to 18 years, because no dosing or adverse eventdata are currently available on the use of sunitiniband/or everolimus in patients <18 years of age, (children are excluded from this study, but will be eligiblefor future paediatric trials). Eastern Cooperative Oncology Group (ECOG)performance status less than and equal to 2 (Karnofsky more than and equal to 60%, see onlinesupplementary appendix A). Patients must have normal organ and bone marrowfunctions as defined below:- Leucocytes: more than and equal to 3000/¦ÌL;- Absolute neutrophil count: more than and equal to 1500/¦ÌL;- Platelets: more than and equal to institutional lotheyr limit of normal;- Total bilirubin: less than and equal to 2fold above institutional upperlimit of normal;- Aspartate aminotransferase (AST) (serum glutamicoxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)): less than and equal to 2.5fold above institutionalupper limit of normal;- Creatinine: within normal institutional limits;- OR- Creatinine clearance: more than and equal to 60 mL/min/1.73 m2 forpatients with creatinine levels above institutionalnormal. Agreement to use effective contraception while ontreatment and for more than and equal to 3 months after end of treatment, because the effects of sunitinib and everolimus onthe developing human fetus are unknown. Should awoman become pregnant or suspect she is pregnantwhile she is participating in this study, she shouldinform her treating physician immediately. Must have fully recovered from toxicities of any priortreatment with cytotoxic drugs, radiotherapy, surgery, or other anticancer modalities (returned to baselinestatus as noted before most recent treatment). Ability of patient or legally authorised representativeto understand, and the willingness to sign a writteninformed consent document. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | everolimus |
| Treatment Info: | Patients will undergo tumour biopsy (if they are not a surgical candidate) for tumour genotyping. Patients will be assigned to sunitininb or everolimus based on somatic/germline mutations profile. Patients who have disease progression on either sunitinib or everolimus will crossover to the other drug. Treatment will continue until disease progression, unacceptable toxicity, or consent to withdrawal. Using the proposed criteria, 44 patients will be accrued within each treatment group during a 48month period (a total of 88 patients for the 2 treatments), and follotheyd for up to an additional 12 months (a total of 60 months from entry of the first patient) to achieve 80% potheyr in order to test whether there is an improvement in PFS compared to historically expected results, with a 0.10 ¦Á level onesided significance test. |
| Primary End Point: | PFS |
| Secondary End Point: | Overall response rate and duration ofresponse;Overall survival (OS) and median survival time.Relationship between tumour genotype, treatmentand PFS. Safety end points |
| Patients Number: | 88 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | NA |