Clinical trial NCT01430416: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Uveal Melanoma
Keywords: Uveal melanoma
phase 1
AEB071
Metastatic
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-09-08
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation
timeFrame: cycle 1 (28 days)
measure: Number of participants reporting serious adverse events and adverse events - Dose Expansion
timeFrame: Baseline, every 28 days
Secondary outcomes:
measure: Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1
timeFrame: Baseline, 12 months
measure: Progression free survival and time to progression using RECIST version 1.1
timeFrame: Baseline, 12 months
measure: Number of patients reporting serious adverse events and adverse events
timeFrame: Baseline, 12 months
measure: AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA
timeFrame: First 7 months of treatment period
measure: Gα genotype in tumor specimens
timeFrame: Baseline, 28 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute DFCI - Brookline
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering MSKCC 4
state: New York
city: Paris
country: France
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: