Viewing Study NCT06502171



Ignite Creation Date: 2024-10-26 @ 3:34 PM
Last Modification Date: 2024-10-26 @ 3:34 PM
Study NCT ID: NCT06502171
Status: NOT_YET_RECRUITING
Last Update Posted: None
First Post: 2024-07-09

Brief Title: Study of Cabozantinib with Selumetinib for Plexiform Neurofibromas
Sponsor: None
Organization: None

Study Overview

Official Title: A Phase 11b2 Study of Cabozantinib in Combination with Selumetinib for Plexiform Neurofibroma in Adults and Adolescents with Neurofibromatosis Type 1
Status: NOT_YET_RECRUITING
Status Verified Date: 2024-07
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: No
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: NF113
Brief Summary: Based on the clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials the demonstrated activity of these agents in reduced doses in preclinical studies and the non-overlapping toxicity profiles the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in participants with NF1 16 years old with progressive andor symptomatic PN in a phase 11b2 clinical trial

Trial Design Phase 1 This will be an open label dose escalation phase Dose level escalation will be determined by a rolling six design In this design up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity DLT within the DLT window The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level

Phase 1b Once the recommended phase 2 dose has been determined in phase 1 an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study

Phase 2 This will be an open label single-arm phase using the recommended phase 2 dose
Detailed Description: Neurofibromatosis type 1 NF1 is one of the most common inherited tumor predisposition syndromes affecting approximately 1 in 3000 people worldwide NF1 is an autosomal dominant condition caused by pathogenic variants in the NF1 tumor suppressor gene resulting in a deficiency in the protein neurofibromin resulting in constitutive activation of the Ras oncoprotein and subsequent tumors Plexiform neurofibromas PN are a complex of Schwann cells fibroblasts endothelial cells and mast cells which can cause disfigurement pain life threatening complications and can undergo malignant transformation These tumors are refractory to most therapeutic approaches including chemotherapy radiation and surgery thus novel treatment interventions are urgently needed Two agents have shown substantial activity in shrinking PN in adults with symptomatic or progressive PN in clinical trials through the NCI and the Congressionally Directed Medical Research Programs CDMRP Neurofibromatosis Clinical Trials Consortium NFCTC the MEK inhibitor selumetinib and the multi-tyrosine kinase inhibitor cabozantinib Unfortunately confirmed objective responses are not uniformly achieved and the degree of volumetric tumor reduction might be improved in patients with partial response as only a small percentage of patients have deep responses In an open-label phase 2 study evaluating selumetinib for children with inoperable PN 68 of participants treated with selumetinib achieved a partial response defined as a reduction in tumor volume by 20 In a phase 2 trial NCT02101736 of cabozantinib in participants 16 years old with symptomatic or progressive PN 42 of patients had a partial response Of note dose reductions andor discontinuation of treatment was common in both studies with 28 of patients in the selumetinib study requiring dose reductions and 10 eventually requiring permanent discontinuation of treatment In the cabozantinib study 42 of the participants required dose reductions or discontinuation of therapy due to either dose-limiting toxicity or low-grade adverse events AEs perceived to be intolerable

Based on the demonstrated significant clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials and the demonstrated activity of these agents in reduced doses in the preclinical studies as well as the non-overlapping toxicity profiles the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in patients with NF1 16 years old with progressive or symptomatic PN in a phase 11b2 clinical trial

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