Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

NCT01430416 | Completed Phase 1

• 2 other identifiers: COEB071X21022011-002535-25
• Study Type: interventional
• Target: 153
• Locations: 4 countries
• Sites: 5

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.

Conditions

Uveal Melanoma

Keywords

Uveal melanoma; phase 1; AEB071; Metastatic

Outcome Measures

Primary Outcomes (2)

• Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation

  cycle 1 (28 days)

• Number of participants reporting serious adverse events and adverse events - Dose Expansion

  Baseline, every 28 days

Secondary Outcomes (5)

• Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1

  Baseline, 12 months

• 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

• AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA

  First 7 months of treatment period

• Gα genotype in tumor specimens

  Baseline, 28 days

Study Arms (1)

AEB071

EXPERIMENTAL

Drug: AEB071

Interventions

AEB071 DRUG

AEB071

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Dana Farber Cancer Institute DFCI - Brookline

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering MSKCC 4

New York, New York, 10017, United States

Location

Novartis Investigative Site

Paris, 75231, France

Location

Novartis Investigative Site

Leiden, 2300 RC, Netherlands

Location

Novartis Investigative Site

London, SW3 6JJ, United Kingdom

Location

Related Links

• Results for COEB071X2102 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis

Interventions

sotrastaurin

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2011
• First Posted: September 8, 2011
• Study Start: December 20, 2011
• Primary Completion: May 22, 2019
• Study Completion: May 22, 2019
• Last Updated: December 19, 2020

Record last verified: 2020-05

Locations

FR (1); GB (1); US (2); NL (1)