Ignite Creation Date:
2024-05-06 @ 7:54 AM
Last Modification Date:
2024-10-26 @ 11:53 AM
Study NCT ID:
NCT02626962
Status:
COMPLETED
Last Update Posted:
2022-03-22
First Post:
2015-12-01
Brief Title:
Trial of Nivolumab in Combination With Ipilimumab in Subjects With Previously Untreated Metastatic Uveal Melanoma
Sponsor:
Grupo Español Multidisciplinar de Melanoma
Organization:
Grupo Español Multidisciplinar de Melanoma
Study Overview
Official Title:
Phase II Multicenter Non Randomized Open Label Trial of Nivolumab in Combination With Ipilimumab in Subjects With Previously Untreated Metastatic Uveal Melanoma
Status:
COMPLETED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GEM1402
Brief Summary:
This is a Phase 2 single-arm study of nivolumab combined with ipilimumab in subjects with previously untreated unresectable or metastatic uveal melanoma Previous studies with immunotherapy have shown promising results and this synergistic combination was very effective in other tumors This study will allow for further characterization of the safety and clinical activity of nivolumab combined with ipilimumab in subjects with uveal melanoma
Detailed Description:
Uveal melanoma is a rare disease accounting for 01 of all cancer deaths This disease arises from melanocytes of the uveal tract and is the most common primary intraocular tumor in adults with an incidence estimated at 06 per 100000 personsyear in the Western population and seems to have remained stable over time
Metastases in uveal melanoma appear in 65-35 of the patients during the first decade The clinical and metastatic behavior differs from cutaneous melanoma because of its initially purely hematogenous dissemination and its tendency to metastasize to the liver Furthermore the liver is almost a sentinel lymph node for uveal melanoma because it is affected in 95 of patients and it is the sole site of metastasis in most cases This specific ocular-hepatic tropism remains unexplained When liver metastases develop the prognosis is poor and life expectancy is reduced to less than 6 months in the absence of treatment Only few prognostic factors for survival have been identified Age short time interval to metastases development and tumor burden in the liver have shown a negative impact on survival whereas patients diagnosed at regular follow-up survive significantly longer probably due to the earlier diagnosis Several loco-regional treatment options can be considered if metastases are confined to the liver including partial hepatic resection or radiofrequency ablation Curative resection is possible in only a small fraction of patients due to the number location or size of the metastases
Systemic chemotherapy is usually unsuccessful in metastatic uveal melanoma and results were recently reviewed showing an Overall Response Rate of 46 with 95 CI 33-63 There is no proof that conventional chemotherapy prolongs survival with most studies reporting OS between 5 and 12 months Most therapies are derived from the experience extrapolated from cutaneous melanoma Only few chemotherapeutic regimens have been studied in phase II trials such as bleomycin vincristine lomustine dacarbazine BOLD fotemustine9-nitrocamptothecin temozolomide bendamustine gemcitabinetreosulfan cisplatingemcitabinetreosulfan and dacarbazinetreosulfan with poor results that range from 0 to 15 response rate and less than 12 months overall survival with first line therapy A phase III trial randomizing patients to chemotherapy or Best Suportive Care BSC is not expected to be performed because of difficulty in recruiting due to the low incidence of disease
In the other hand the best understanding of the biology of cancer disease has allowed us to identify pathways that are important in mechanisms of proliferation survival or dissemination Recently Guanine Nucleotide-Binding Protein G GNAQ gene oncogenic mutation has been identified in close to 50 of primary uveal melanomas The emergence of newer agents that target this or other pathways such as selumetinib sunitinib imatinib vorinostat antiangiogenics have resulted in multiple small studies that up to date have failed to show a clear superiority against chemotherapy To summarize patients with metastatic uveal melanoma should be included in clinical trials evaluating other options with newer agents with potentially less toxicity and greater efficacy than conventional chemotherapy
Metastases in uveal melanoma appear in 65-35 of the patients during the first decade The clinical and metastatic behavior differs from cutaneous melanoma because of its initially purely hematogenous dissemination and its tendency to metastasize to the liver Furthermore the liver is almost a sentinel lymph node for uveal melanoma because it is affected in 95 of patients and it is the sole site of metastasis in most cases This specific ocular-hepatic tropism remains unexplained When liver metastases develop the prognosis is poor and life expectancy is reduced to less than 6 months in the absence of treatment Only few prognostic factors for survival have been identified Age short time interval to metastases development and tumor burden in the liver have shown a negative impact on survival whereas patients diagnosed at regular follow-up survive significantly longer probably due to the earlier diagnosis Several loco-regional treatment options can be considered if metastases are confined to the liver including partial hepatic resection or radiofrequency ablation Curative resection is possible in only a small fraction of patients due to the number location or size of the metastases
Systemic chemotherapy is usually unsuccessful in metastatic uveal melanoma and results were recently reviewed showing an Overall Response Rate of 46 with 95 CI 33-63 There is no proof that conventional chemotherapy prolongs survival with most studies reporting OS between 5 and 12 months Most therapies are derived from the experience extrapolated from cutaneous melanoma Only few chemotherapeutic regimens have been studied in phase II trials such as bleomycin vincristine lomustine dacarbazine BOLD fotemustine9-nitrocamptothecin temozolomide bendamustine gemcitabinetreosulfan cisplatingemcitabinetreosulfan and dacarbazinetreosulfan with poor results that range from 0 to 15 response rate and less than 12 months overall survival with first line therapy A phase III trial randomizing patients to chemotherapy or Best Suportive Care BSC is not expected to be performed because of difficulty in recruiting due to the low incidence of disease
In the other hand the best understanding of the biology of cancer disease has allowed us to identify pathways that are important in mechanisms of proliferation survival or dissemination Recently Guanine Nucleotide-Binding Protein G GNAQ gene oncogenic mutation has been identified in close to 50 of primary uveal melanomas The emergence of newer agents that target this or other pathways such as selumetinib sunitinib imatinib vorinostat antiangiogenics have resulted in multiple small studies that up to date have failed to show a clear superiority against chemotherapy To summarize patients with metastatic uveal melanoma should be included in clinical trials evaluating other options with newer agents with potentially less toxicity and greater efficacy than conventional chemotherapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2015-004429-15 | EUDRACT_NUMBER | None | None |