Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

Phase 1

Completed

• Conditions: Uveal Melanoma
• Interventions: Drug: AEB071

• Registration Number: NCT01430416
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-06
• Study First Submitted QC: 2011-09-07
• Study First Posted: 2011-09-08
• Study Start: 2011-12-20
• Primary Completion: 2019-05-22
• Study Completion: 2019-05-22
• Status Verified: 2020-05
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 153

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AEB071	AEB071	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Gα genotype in tumor specimens	Baseline, 28 days
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
Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1	Baseline, 12 months
AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA	First 7 months of treatment period

Trial Locations

Locations (3)

Memorial Sloan Kettering MSKCC 4; 🇺🇸 New York, New York, United States

Novartis Investigative Site; 🇬🇧 London, United Kingdom

Dana Farber Cancer Institute DFCI - Brookline; 🇺🇸 Boston, Massachusetts, United States