F16IL2 Plus Paclitaxel in Metastatic Merkel Cell Carcinoma

Merkel Cell Carcinoma Clinical Trial

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

Clinical Trial Summary

There is no standard treatment for Merkel cell carcinoma(MCC), 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).

Clinical Trial Description

F16IL2 has been studied in two clinical pase I/II 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 mg/m2 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 F16IL2/paclitaxel 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 F16IL2/paclitaxel combination trial(particularly 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. ScFv(F16) 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, monocyte/macrophages and neutrophils (Smith, 1988). IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo (Rosenberg, 2000). ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Merkel Cell
• Merkel Cell Carcinoma

• NCT number: NCT02054884
• Study type: Interventional
• Source: Philogen S.p.A.
• Status: Terminated
• Phase: Phase 2
• Start date: October 25, 2013
• Completion date: December 15, 2017