Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Eye Diseases

Rare Diseases

Melanoma

Uveal Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Ocular Melanoma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

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

AEB071

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

MEK162

Pfizer CT.gov Call Center

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

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

Remaining patients on treatment with binimetinib and sotrastaurin who were considered by the Investigator to be benefiting from their treatment could have continued treatment and were to be followed up as per protocol. No patients were ongoing as of the data cut-off date. After the last patient last visit (LPLV) was declared, the study was terminated.

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

A Phase Ib/II, Open-label, Multicenter Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma

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.

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.

An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.

Serious adverse event (SAE) is defined as one of the following:

* Is fatal or life-threatening
* Results in persistent or significant disability/incapacity
* Constitutes a congenital anomaly/birth defect
* Is medically significant
* Requires inpatient hospitalization or prolongation of existing hospitalization
* Note that hospitalizations for the following reasons should not be reported as serious adverse events:

  * Routine treatment or monitoring of the studied indication, not associated with any deterioration in condition
  * Elective or pre-planned treatment for a pre-existing condition that is unrelated to metastatic uveal melanoma and has not worsened since signing the informed consent
  * Social reasons and respite care in the absence of any deterioration in the patient's general condition

Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination.

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination.

Duration of Response (DOR) is not reported, since there were no responses of Complete Response (CR) or Partial Response (PR) at any time during the study.

Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination.

PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.

Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone.

Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR). This is also referred to as 'Objective response rate' in some protocols or publications.

Due to an enrollment halt, the Phase II part of the study was not conducted.

Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone.

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Progressive Disease (PD) the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

Due to an enrollment halt, the Phase II part of the study was not conducted.

Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone.

Duration of Response is not reported, due to the enrollment halt, which occurred prior to Phase II of the study.

Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone.

Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause.

Due to an enrollment halt, the Phase II part of the study was not conducted.

Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.

Array Biopharma, now a wholly owned subsidiary of Pfizer

AE reporting is comprised of the Safety Set (SS), which is all patients who received at least one dose of AEB071 and MEK162, and have at least one valid post-baseline safety assessment.

Phase Ib (Dose Escalation)

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS)

Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS)

Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS)

Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS)

Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS)

Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS)

Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS)

Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS)

Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Hispanic or Latino

Russian

Unknown

Other

Race/Ethnicity, Customized

Netherlands

United States

United Kingdom

France

Germany

Spain

Region of Enrollment

Categories:

* 0 - Fully active, able to carry on all pre-disease performance without restriction
* 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
* 2 - Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
* 3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
* 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

Baseline WHO Performance Status

Baseline Demographics data represents the Full Analysis Set (FAS), which includes all patients who received at least one full or partial dose of sotrastaurin or binimetinib.

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.

Study Director

Anaemia

Diarrhoea

Vomiting

Nausea

Fatigue

General Physical Health Deterioration

Malaise

Blood Creatinine Increased

Ejection Fraction Decreased

Dermatitis Acneiform

Rash

Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS)

Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS)

Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS)

Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS)

Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS)

Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS)

Analysis is comprised of the Dose-determining Set, which is all patients from the safety set who either met the minimum exposure criterion below and had sufficient safety evaluations during Cycle 1, or discontinued earlier due to DLT during Cycle 1.

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

Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur.

Phase II (Dose Expansion)

Phase II: Progression Free Survival (PFS)

Analysis group consists of the Safety Set (SS), which is all patients who received at least one dose of AEB071 and MEK162, and have at least one valid post-baseline safety assessment.

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

Analysis group is comprised of the Safety Set (SS), which is all patients who received at least one dose of AEB071 and MEK162, and have at least one valid post-baseline safety assessment.

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

Complete Response

Partial Response

Stable Disease

Progressive disease

Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162.

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

For Phase Ib, a minimum of three patients will be entered into each cohort and evaluated for safety (DLTs and any other medically significant event) at the end of Cycle 1.

Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.

Phase Ib (Dose Escalation)

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

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

Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR)

Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR)

Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR)

Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS)

Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS)

Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS)

Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS)

Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS)

Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS)

Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS)

This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data.

Spots Global Cancer Trial Database for A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial