NCT02273219

Brief Summary

Primary objective is to define the maximum tolerated dose (MTD) for the combination of AEB071 and BYL719. Secondary objectives are to define the safety and tolerability of AEB071 and BYL719.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2014

Typical duration for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 17, 2014

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 23, 2014

Completed
27 days until next milestone

Study Start

First participant enrolled

November 19, 2014

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 18, 2017

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 2, 2018

Completed
Last Updated

August 15, 2023

Status Verified

August 1, 2023

Enrollment Period

2.9 years

First QC Date

October 17, 2014

Last Update Submit

August 11, 2023

Conditions

Uveal Melanoma

Keywords

UvealMelanomaAdvanced uveal melanoma

Outcome Measures

Primary Outcomes (1)

  • Total maximum tolerated dose (in milligrams) of AEB071 in combination with BYL719

    Establish the maximum tolerated dose (up to 400 mg twice daily) for AEB071 and up to 350 mg daily for BYL719

    4 years (approximately)

Secondary Outcomes (6)

  • Number of participants with adverse events

    4 years (approximately)

  • Change in area under the curve (AUC) for the combination of AEB071 and BYL719

    Cycle 1 Day 1, pre-dose, .5, 1, 2, 4, 6, 8, and 24 hours post dose, Cycle 1, Day 8, pre-dose, .5, 1, 2, 4, 6, and 8 hours post dose, Cycle 1 Day 15, pre-dose, Cycle 2-3-4-5-6 Day 1, pre-dose

  • Change in peak concentration (Cmax) for the combination of AEB071 and BYL719

    Cycle 1 Day 1, pre-dose, .5, 1, 2, 4, 6, 8, and 24 hours post dose, Cycle 1, Day 8, pre-dose, .5, 1, 2, 4, 6, and 8 hours post dose, Cycle 1 Day 15, pre-dose, Cycle 2-3-4-5-6 Day 1, pre-dose

  • Number participants who respond to therapy

    4 years (approximately)

  • Change in numerically calculated toxicity burden (0-10)

    baseline, Cycle 1 Day 8, Day 15, and Day 22, Cycle 2 and above, End of Treatment, 28 day Follow-Up visit

  • +1 more secondary outcomes

Study Arms (5)

Dose 1: AEB071 and BYL719

EXPERIMENTAL

AEB071, oral, 100 mg twice daily BYL719, oral, 200 mg daily

Drug: AEB071Drug: BYL719

Dose 2: AEB071 and BYL719

EXPERIMENTAL

AEB071, oral, 200 mg twice daily BYL719, oral, 250 mg daily

Drug: AEB071Drug: BYL719

Dose 3: AEB071 and BYL719

EXPERIMENTAL

AEB071, oral, 200 mg twice daily BYL719, oral, 300 mg daily

Drug: AEB071Drug: BYL719

Dose 4: AEB071 and BYL719

EXPERIMENTAL

AEB071, oral, 200 mg twice daily BYL719, oral, 350 mg daily

Drug: AEB071Drug: BYL719

Dose 5: AEB071 and BYL719

EXPERIMENTAL

AEB071, oral, 300 mg twice daily BYL719, oral, 350 mg daily

Drug: AEB071Drug: BYL719

Interventions

AEB071DRUG

Oral, 100-400 mg twice daily A potent, oral, selective inhibitor of the classical Protein Kinase C (PKC)

Also known as: Sotrastaurin
Dose 1: AEB071 and BYL719Dose 2: AEB071 and BYL719Dose 3: AEB071 and BYL719Dose 4: AEB071 and BYL719Dose 5: AEB071 and BYL719
BYL719DRUG

Oral, 200-350 mg daily An oral class I α-specific PI3K inhibitor belonging to the 2-aminothiazole class of compounds

Also known as: NVP-BYL719
Dose 1: AEB071 and BYL719Dose 2: AEB071 and BYL719Dose 3: AEB071 and BYL719Dose 4: AEB071 and BYL719Dose 5: AEB071 and BYL719

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Metastatic histologically or cytologically confirmed uveal melanoma with pathologic confirmation at a participating center that is judged to be progressive in the opinion of the treating physician.
  • Measurable disease. Patients with biopsy-proven metastatic disease that do not meet criteria for measurable disease may be eligible at the discretion of the principal investigator.
  • Prior cytotoxic therapy and immunotherapy are allowed. For the dose escalation, prior targeted therapy with a MEK inhibitor, Protein Kinase C inhibitor, Akt, or mechanistic target of rapamycin (mTOR) inhibitor are allowed. For the dose expansion cohort, no prior PKC, Akt, or mTOR inhibitors are allowed. Local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least 21 days prior to initiation of study therapy.
  • Age greater than or equal to 18 years
  • Willingness to undergo core biopsies at baseline, mid-Cycle 1, and/or at progression unless contraindicated by medical risk in the opinion of the treating physician.
  • Easter Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent).
  • Life expectancy of greater than 3 months.
  • Able to swallow and retain medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • Fasting plasma glucose (FPG) less than 140 mg/dL / 7.8 mmol/L.
  • All prior treatment-related toxicities must be grade less than or equal to 1 (except alopecia).
  • Patients must have adequate organ and marrow function within 14 days of starting Cycle 1, Day 1 of therapy
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to registration.
  • Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

  • History of another malignancy except for those who have been disease-free for 24 months. Patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies not requiring active therapy are eligible.
  • Any major surgery or extensive radiotherapy within 28 days prior to screening
  • Use of other investigational drugs within 28 days (or five half-lives, whichever is longer) preceding the first dose of AEB071 and BYL719.
  • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases must have been stable for at least 1 month.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to AEB071 or BYL719.
  • Current use of a prohibited medication.
  • Type I Diabetes Mellitus (DM), Type II DM patients requiring insulin for chronic blood glucose control, and any patients with a fasting blood glucose greater than 140 mg/dL at screening.
  • History or evidence of cardiovascular risk.
  • Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection, which will be allowed).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with impairment of gastrointestinal function or gastrointestinal disease that could interfere with the absorption of AEB071 or BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patients who have received prior systemic anti-cancer treatment, such as cyclical chemotherapy or biological therapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Bascom Palmer Eye Institute of University Of Miami Medical Center

Miami, Florida, 33136, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Uveal MelanomaMelanoma

Interventions

sotrastaurinAlpelisib

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasUveal NeoplasmsEye NeoplasmsNeoplasms by SiteEye DiseasesUveal DiseasesSkin NeoplasmsSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Richard Carvajal, MD

    Columbia University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 17, 2014

First Posted

October 23, 2014

Study Start

November 19, 2014

Primary Completion

October 18, 2017

Study Completion

July 2, 2018

Last Updated

August 15, 2023

Record last verified: 2023-08

Locations

US(3)