Back to resultsSafety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients
Primary Purpose
Uveal Melanoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AEB071
Sponsored by
About this trial
This is an interventional treatment trial for Uveal Melanoma focused on measuring Uveal melanoma, phase 1, AEB071, Metastatic
Eligibility Criteria
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
Sites / Locations
- Dana Farber Cancer Institute DFCI - Brookline
- Memorial Sloan Kettering MSKCC 4
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AEB071
Arm Description
Outcomes
Primary Outcome Measures
Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation
Number of participants reporting serious adverse events and adverse events - Dose Expansion
Secondary Outcome Measures
Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1
Progression free survival and time to progression using RECIST version 1.1
Number of patients reporting serious adverse events and adverse events
AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA
Gα genotype in tumor specimens
Full Information
NCT ID
NCT01430416
First Posted
September 6, 2011
Last Updated
December 16, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01430416
Brief Title
Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients
Official Title
A Phase 1 Study of AEB071, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
December 20, 2011 (Actual)
Primary Completion Date
May 22, 2019 (Actual)
Study Completion Date
May 22, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveal Melanoma
Keywords
Uveal melanoma, phase 1, AEB071, Metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
153 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AEB071
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AEB071
Primary Outcome Measure Information:
Title
Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation
Time Frame
cycle 1 (28 days)
Title
Number of participants reporting serious adverse events and adverse events - Dose Expansion
Time Frame
Baseline, every 28 days
Secondary Outcome Measure Information:
Title
Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1
Time Frame
Baseline, 12 months
Title
Progression free survival and time to progression using RECIST version 1.1
Time Frame
Baseline, 12 months
Title
Number of patients reporting serious adverse events and adverse events
Time Frame
Baseline, 12 months
Title
AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA
Time Frame
First 7 months of treatment period
Title
Gα genotype in tumor specimens
Time Frame
Baseline, 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Dana Farber Cancer Institute DFCI - Brookline
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Memorial Sloan Kettering MSKCC 4
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75231
Country
France
Facility Name
Novartis Investigative Site
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17658
Description
Results for COEB071X2102 can be found on the Novartis Clinical Trial Results Website
Learn more about this trial
Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients
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