Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

A Phase 1 Study of AEB071, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma

This study has two parts, dose escalation and dose expansion. For dose escalation, the primary objective is to estimate the maximum tolerated dose (MTD) of AEB071 in patients with uveal melanoma. For dose expansion, the primary objective is to characterize the safety and tolerability of the MTD of AEB071 in patients with uveal melanoma.

Study Overview

• Status: Completed
• Conditions: Uveal Melanoma
• Intervention / Treatment: Drug: AEB071

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75231
    • Novartis Investigative Site
• Netherlands
  • Leiden, Netherlands, 2300 RC
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute DFCI - Brookline
  • New York
    • New York, New York, United States, 10017
      • Memorial Sloan Kettering MSKCC 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Uveal melanoma with biopsy proven metastatic disease
• Males and females ≥ 18 years of age
• Consent to biopsy of tumor
• Measurable disease according to RECIST version 1.1
• WHO performance status of ≤ 1

Exclusion Criteria:

• Patients with abnormal laboratory values as defined by the protocol
• Patients who are receiving treatment with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued prior to study entry
• Patients with impaired cardiac function or clinically significant cardiac diseases as defined by the protocol
• Patients with another malignancy that was treated within the last three years with the exceptions of localized basal cell carcinoma and cervical carcinoma
• Patients with impairment of gastrointestinal function or disease
• Patients with severe systemic infections
• Patients who are known to be HIV positive and/or have active hepatitis B or C infection

• Time since last therapy for treatment of underlying malignancy:

  • Cytotoxic chemotherapy: ≤ duration of the most recent cycle of the previous regimen (a minimum of 2 weeks for all)
  • Nitrosurea: ≤ 6 weeks
  • Biologic therapy: ≤ 4 weeks
  • ≤ 5 x PK half-life of a small molecule therapeutic not otherwise defined above
• Patients having undergone major surgery less than 4 weeks prior to enrollment or have not fully recovered from prior surgery
• Women of child-bearing potential unless they are using highly effective methods of contraception during the dosing and for at least 36 hours after last dose. Highly effective contraception as defined in the protocol.
• Patients with primary central nervous system tumors or brain metastases.
• Pregnant or nursing (lactating) women.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AEB071	Drug: AEB071

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation	cycle 1 (28 days)
Number of participants reporting serious adverse events and adverse events - Dose Expansion	Baseline, every 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1	Baseline, 12 months
Progression free survival and time to progression using RECIST version 1.1	Baseline, 12 months
Number of patients reporting serious adverse events and adverse events	Baseline, 12 months
AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA	First 7 months of treatment period
Gα genotype in tumor specimens	Baseline, 28 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for COEB071X2102 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2011
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): May 22, 2019

Study Registration Dates

• First Submitted: September 6, 2011
• First Submitted That Met QC Criteria: September 7, 2011
• First Posted (Estimate): September 8, 2011

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: phase 1; Metastatic; Uveal melanoma; AEB071
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uveal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Melanoma; Uveal Neoplasms
• Other Study ID Numbers: COEB071X2102; 2011-002535-25 (EudraCT Number)