Ignite Creation Date:
2024-05-06 @ 2:29 AM
Last Modification Date:
2024-10-26 @ 11:19 AM
Study NCT ID:
NCT02054884
Status:
TERMINATED
Last Update Posted:
2018-05-18
First Post:
2014-01-31
Brief Title:
F16IL2 Plus Paclitaxel in Metastatic Merkel Cell Carcinoma
Sponsor:
Philogen SpA
Organization:
Philogen SpA
Study Overview
Official Title:
Phase II Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Paclitaxel in Patients With Metastatic Merkel Cell Carcinoma
Status:
TERMINATED
Status Verified Date:
2018-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
There is no standard treatment for Merkel cell carcinomaMCC as no randomized trials have been conducted to establish standard of care Despite a sizable number of objective responses induced by combination cyototoxic chemotherapy a prolongation of patients overall survival has never been demonstrated
This open-label randomized double-arm multi-centre phase II study of F16IL2 in combination with paclitaxel versus paclitaxel monotherapy proposes to test the therapeutic efficacy of F16IL2 plus paclitaxel in patients with metastatic Merkel cell carcinoma who are not amenable to surgery
A total of 90 patients with Merkel cell carcinoma will be enrolled and treated during the study 45 patients will receive the combination treatment of F16IL2 and paclitaxel Arm A and 45 patients will receive paclitaxel monotherapy Arm B
This open-label randomized double-arm multi-centre phase II study of F16IL2 in combination with paclitaxel versus paclitaxel monotherapy proposes to test the therapeutic efficacy of F16IL2 plus paclitaxel in patients with metastatic Merkel cell carcinoma who are not amenable to surgery
A total of 90 patients with Merkel cell carcinoma will be enrolled and treated during the study 45 patients will receive the combination treatment of F16IL2 and paclitaxel Arm A and 45 patients will receive paclitaxel monotherapy Arm B
Detailed Description:
F16IL2 has been studied in two clinical pase III trials in patients with different advanced cancer types One of them Nr EudraCT 2007-006457-42 tested the administration of therapeutic doses of paclitaxel up to 90 mgm2 on a weekly basis together with escalating doses of F16IL2 from 5 Mio IU of IL2 equivalents in a weekly administration schedule until definition of MTD More than 40 patients were treated in this clinical trial As of today the highest F16IL2 dose tested corresponds to 45 Mio IU but the dose escalataion of the F16IL2paclitaxel combination study is still ongoing
In general treatment of patients with F16IL2 plus paclitaxel was very well tolerated not exceeding the expected toxicity of chemotherapy alone Multiple objective and durable tumor responses were observed in the F16IL2paclitaxel combination trialparticularly in patients with non small cell lung cancer or melanoma who had previously failed several lines of chemotherapy In addition to several disease stabilizations of previously progressive patients
Paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerisation This stability results in the inhibition of the normal reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions In addition paclitaxel reduces abnormal arrays or bundles of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis
F16 is a human recombinant antibody fragment in the scFv single chain Fragment variable format that is directed against tenascin C an angiogenesis marker common to most solid tumors independent of the tumor type ScFvF16 selectively localizes in tumor tissues in animal models as demonstrated both histologically and during mechanistic studies involving mice transfected with orthotopic human tumours
IL2 the human cytokine interleukin-2 is a potent stimulator of the immune response It has a central role in the regulation of T cell responses and effects on other immune cells such as natural killer cells B cells monocytemacrophages and neutrophils Smith 1988 IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo Rosenberg 2000
In general treatment of patients with F16IL2 plus paclitaxel was very well tolerated not exceeding the expected toxicity of chemotherapy alone Multiple objective and durable tumor responses were observed in the F16IL2paclitaxel combination trialparticularly in patients with non small cell lung cancer or melanoma who had previously failed several lines of chemotherapy In addition to several disease stabilizations of previously progressive patients
Paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerisation This stability results in the inhibition of the normal reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions In addition paclitaxel reduces abnormal arrays or bundles of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis
F16 is a human recombinant antibody fragment in the scFv single chain Fragment variable format that is directed against tenascin C an angiogenesis marker common to most solid tumors independent of the tumor type ScFvF16 selectively localizes in tumor tissues in animal models as demonstrated both histologically and during mechanistic studies involving mice transfected with orthotopic human tumours
IL2 the human cytokine interleukin-2 is a potent stimulator of the immune response It has a central role in the regulation of T cell responses and effects on other immune cells such as natural killer cells B cells monocytemacrophages and neutrophils Smith 1988 IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo Rosenberg 2000
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