Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01430416

Collaborator

(none)

153

Enrollment

Locations

Arm

Actual Duration (Months)

30.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Uveal Melanoma	Drug: AEB071	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

153 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 20, 2011

Actual Primary Completion Date :

May 22, 2019

Actual Study Completion Date :

May 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AEB071	Drug: AEB071

Arm

Intervention/Treatment

Experimental: AEB071

Drug: AEB071

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute DFCI - Brookline	Boston	Massachusetts	United States	02215
2	Memorial Sloan Kettering MSKCC 4	New York	New York	United States	10017
3	Novartis Investigative Site	Paris		France	75231
4	Novartis Investigative Site	Leiden		Netherlands	2300 RC
5	Novartis Investigative Site	London		United Kingdom	SW3 6JJ