A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma

NCT01801358 | Terminated Phase 1 Results

• 1 other identifier: CMEK162X2203
• Study Type: interventional
• Target: 38
• Locations: 6 countries
• Sites: 7

Brief Summary

A phase Ib dose-escalation study of the AEB071 and MEK162 combination in adult patients with confirmed metastatic uveal melanoma. Cohorts of 3-6 patients will be assessed for dose limiting toxicities (DLTs) during Cycle 1 until the maximum tolerated dose (MTD) of the combination therapy is determined. The MTD or Phase 2 Recommended Dose (P2RD) will be used in a Phase II part of the study, which will enrol 55 patients each into two randomized groups: the combination therapy or MEK162 alone. The Phase II part will continue until proof of concept is established. Patients will continue treatment as long as clinical benefit is seen and no limiting adverse toxicity is observed

Conditions

Uveal Melanoma

Keywords

Melanoma,; melanoma of the eye,; uveal,; MEK162,; AEB071

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle

  A DLT is defined as an adverse event or abnormal laboratory value as defined in the protocol that is assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with AEB071 and MEK162.

  Cycle 1 (up to 28 days)

• Phase II: Progression Free Survival (PFS)

  The time from date of randomization to the date of event defined as the first documented progression or death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination.

  From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)

Secondary Outcomes (21)

• Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE)

  From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)

• Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE)

  From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)

• Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR)

  Cycle 1 (up to 28 days)

• Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR)

  Cycle 1 (up to 28 days)

• Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS)

  Cycle 1 (up to 28 days)

Study Arms (2)

Arm A

EXPERIMENTAL

AEB071 and MEK162 combined

Drug: AEB071; Drug: MEK162

Arm B

EXPERIMENTAL

MEK162 alone

Drug: MEK162

Interventions

AEB071 DRUG

Twice-daily doses of AEB071 for a cycle of 28-days, given without interruption (continuous cycles)

Also known as: Sotrastaurin

Arm A

MEK162 DRUG

Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Male and female patients aged 18 years or older
• A history of uveal (ocular) melanoma with biopsy-confirmed metastatic disease
• Consent to providing 3 tumor biopsy samples throughout the course of the study
• Presence of measurable disease
• A WHO performance status of less than or equal to 1

You may not qualify if:

• Presence of CNS lesions (stable lesions may be acceptable)
• Previous or concurrent malignancy, other than basal cell or squamous cell carcinoma of the skin: in situ carcinoma of the cervix, without evidence of recurrence for at least 3 years; a primary malignancy completely resected and no evidence of recurrence for at least 3 years
• Adverse event from prior chemotherapy, radiotherapy or surgery that has not recovered to CTCAE v4.03 Grade 1 or less, except for alopecia/sensory peripheral neuropathy, which must be less than Grade 2
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
• Impaired cardiac function or clinically significant cardiac disease
• Impaired GI function or disease that could interfere with the absorption of AEB071 and/or MEK162
• Treatment with medicines or herbal supplements that are known inhibitors or inducers of CYP3A4/5 and cannot be withdrawn prior to study treatment
• Females of child-bearing potential who are unwilling or unable to use highly effective means of contraception
• Males who are unwilling or unable to use a condom during sexual intercourse

Sponsors & Collaborators

• Array Biopharma, now a wholly owned subsidiary of Pfizer: lead

Study Sites (7)

Dana Farber Cancer Institute Dept. Onc

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center Dept of Onc..

New York, New York, 90033, United States

Location

Pfizer Investigative Site

Paris, 75231, France

Location

Pfizer Investigative Site

Essen, 45147, Germany

Location

Pfizer Investigative Site

Leiden, 2300 RC, Netherlands

Location

Pfizer Investigative Site

Madrid, 28050, Spain

Location

Pfizer Investigative Site

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

sotrastaurin; binimetinib

Condition Hierarchy (Ancestors)

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; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination.

Results Point of Contact

• Title: Study Director
• Organization: Array BioPharma, Inc.

clinicaltrials@arraybiopharma.com

303-381-6604

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: February 28, 2013
• Study Start: August 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: September 16, 2020
• Results First Posted: October 20, 2016

Record last verified: 2020-09

Locations

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