Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01430416
First received: September 6, 2011
Last updated: June 18, 2014
Last verified: June 2014
  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 and to further explore safety and efficacy in expansion groups at doses lower than the MTD of AEB071 in order to determine the recommended phase 2 dosein 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: 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:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation [ Time Frame: cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
  • Number of participants reporting serious adverse events and adverse events - Dose Expansion [ Time Frame: Baseline, every 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
  • Progression free survival and time to progression using RECIST version 1.1 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
  • Number of patients reporting serious adverse events and adverse events [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: Yes ]
  • AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA [ Time Frame: First 7 months of treatment period ] [ Designated as safety issue: No ]
  • Gα genotype in tumor specimens [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: December 2011
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AEB071 Drug: AEB071

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  • Evaluable disease (escalation part only) or measurable disease according to RECIST v1.1
  • 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

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Massachusetts
Dana Farber Cancer Institute DFCI - Brookline Recruiting
Boston, Massachusetts, United States, 02115
Contact: Maria Gargano    617-582-7116    Maria_Gargano@DFCI.HARVARD.EDU   
Principal Investigator: Stephan Hodi         
United States, New York
Memorial Sloan Kettering Cancer Center MSKCC 4 Recruiting
New York, New York, United States, 10021
Contact: Bernadette Loughlin       loughlib@mskcc.org   
Principal Investigator: Gary K. Schwartz         
France
Novartis Investigative Site Recruiting
Paris, France, 75231
Netherlands
Novartis Investigative Site Recruiting
Leiden, Netherlands, 2300 RC
United Kingdom
Novartis Investigative Site Active, not recruiting
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01430416     History of Changes
Other Study ID Numbers: COEB071X2102, 2011-002535-25
Study First Received: September 6, 2011
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration
France: AFSSAPS
Netherlands: Medicines Evaluation Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Uveal melanoma
phase 1
AEB071
Metastatic

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

ClinicalTrials.gov processed this record on August 28, 2014