Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients - Full Text View

Purpose

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	Intervention	Phase
Uveal Melanoma	Drug: AEB071	Phase 1


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

Genetic and Rare Diseases Information Center resources: Intraocular Melanoma Carcinoid Tumor Neuroepithelioma Uveal Diseases

U.S. FDA Resources

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:

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

Secondary Outcome Measures:

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


Enrollment:	153
Actual Study Start Date:	December 20, 2011
Estimated Study Completion Date:	October 15, 2017
Estimated Primary Completion Date:	October 15, 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AEB071	Drug: AEB071

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01430416

Locations


United States, Massachusetts
Dana Farber Cancer Institute DFCI - Brookline
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center MSKCC 4
New York, New York, United States, 10065
France
Novartis Investigative Site
Paris, France, 75231
Netherlands
Novartis Investigative Site
Leiden, Netherlands, 2300 RC
United Kingdom
Novartis Investigative Site
London, United Kingdom, SW3 6JJ

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01430416 History of Changes
Other Study ID Numbers:	COEB071X2102 2011-002535-25 ( EudraCT Number )
Study First Received:	September 6, 2011
Last Updated:	May 9, 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):


Uveal melanoma phase 1 AEB071 Metastatic

Additional relevant MeSH terms:


Melanoma Uveal Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms	Neoplasms, Nerve Tissue Nevi and Melanomas Eye Neoplasms Neoplasms by Site Eye Diseases Uveal Diseases

ClinicalTrials.gov processed this record on September 21, 2017