Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
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 :	December 20, 2011
Estimated Primary Completion Date :	October 15, 2017
Estimated Study Completion Date :	October 15, 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: AEB071	Drug: AEB071

Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01430416 History of Changes
Other Study ID Numbers:	COEB071X2102; 2011-002535-25 ( EudraCT Number )
First Posted:	September 8, 2011
Last Update Posted:	May 10, 2017
Last Verified:	May 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