Uveal MelanomaPhase 1NCT02273219
Trial of AEB071 in Combination With BYL719 in Patients With Melanoma
A Phase 1 study testing AEB071 and BYL719 in people with Uveal Melanoma, run by Columbia University at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- AEB071 and BYL719
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- 19 Nov 2014to 2 Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Bascom Palmer Eye Institute of University Of Miami Medical Center
Miami, Florida, 33136
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase Ib Trial of AEB071, a PKC Inhibitor, in Combination With BYL719, a PI3Kα Inhibitor, in Patients With Metastatic Uveal Melanoma
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.
Read the detailed description
Uveal melanoma is the most common primary intraocular malignancy in adults and is thought to be particularly resistant to systemic treatment, and no systemic therapy has yet been demonstrated to improve survival. Drugs commonly used to treat advanced cutaneous melanoma rarely achieve durable responses in patients with uveal melanoma. Because of the lack of effective systemic treatment options, outcomes are poor once metastatic disease occurs, and the median survival from the time of the development of distant metastatic disease is 6 to 12 months. Although it is clear that novel effective therapies are desperately needed for this disease, the development of such therapies has been hampered by the rarity of uveal melanoma.
- Conditions
- Uveal Melanoma
- Being tested
- AEB071, BYL719
- Keywords
- Uveal, Melanoma, Advanced uveal melanoma
- Medical subject headings
- Uveal Melanoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AEB071Drug
Also called Sotrastaurin
Oral, 100-400 mg twice daily A potent, oral, selective inhibitor of the classical Protein Kinase C (PKC)
BYL719Drug
Also called NVP-BYL719
Oral, 200-350 mg daily An oral class I α-specific PI3K inhibitor belonging to the 2-aminothiazole class of compounds
| Study group | Role | What they receive |
|---|---|---|
| Dose 1: AEB071 and BYL719 | Experimental | AEB071, oral, 100 mg twice daily BYL719, oral, 200 mg daily Receives: Drug: AEB071; Drug: BYL719 |
| Dose 2: AEB071 and BYL719 | Experimental | AEB071, oral, 200 mg twice daily BYL719, oral, 250 mg daily Receives: Drug: AEB071; Drug: BYL719 |
| Dose 3: AEB071 and BYL719 | Experimental | AEB071, oral, 200 mg twice daily BYL719, oral, 300 mg daily Receives: Drug: AEB071; Drug: BYL719 |
| Dose 4: AEB071 and BYL719 | Experimental | AEB071, oral, 200 mg twice daily BYL719, oral, 350 mg daily Receives: Drug: AEB071; Drug: BYL719 |
| Dose 5: AEB071 and BYL719 | Experimental | AEB071, oral, 300 mg twice daily BYL719, oral, 350 mg daily Receives: Drug: AEB071; Drug: BYL719 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 years (approximately)
Secondary outcomes (6)
Number of participants with adverse events
Obtain safety data of the combination therapy of AEB071 with BYL719
Measured: 4 years (approximately)
Change in area under the curve (AUC) for the combination of AEB071 and BYL719
To evaluate the pharmacokinetic properties of the combination of AEB071 and BYL719 at varying dose levels utilizing standard pharmacokinetic parameters such as peak concentration (Cmax) and area under the curve (AUC) of AEB071 and BYL719 in plasma samples.
Measured: 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
To evaluate the pharmacokinetic properties of the combination of AEB071 and BYL719 at varying dose levels utilizing standard pharmacokinetic parameters such as peak concentration (Cmax) and area under the curve (AUC) of AEB071 and BYL719 in plasma samples.
Measured: 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
Clinical benefit rate will be assessed as overall object response rate, using metric measurements on imaging scans.
Measured: 4 years (approximately)
Change in numerically calculated toxicity burden (0-10)
To explore the toxicity burden on the patient during treatment as perceived by the patient and the physician.
Measured: baseline, Cycle 1 Day 8, Day 15, and Day 22, Cycle 2 and above, End of Treatment, 28 day Follow-Up visit
Mean months of overall survival
Overall survival will be calculated in months, starting at time of enrollment.
Measured: 4 years (approximately)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2014 (estimated)
- Study start19 Nov 2014
- Primary completion18 Oct 2017
- Study completion2 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard Carvajal, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02273219
- Sponsor's protocol ID
- AAAN4901
- Other IDs
- CAEB071AUS01T
- Status last verified
- Aug 2023
- First submitted
- 17 Oct 2014
- Last updated
- 15 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Trial of AEB071, a PKC Inhibitor, in Combination With BYL719, a PI3Kα Inhibitor, in Patients With Metastatic Uveal Melanoma
- ClinicalTrials.gov ID
- NCT02273219
- Acronym / sponsor ID
- AAAN4901
- Conditions
- Uveal Melanoma
- Keywords
- Uveal, Melanoma, Advanced uveal melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 19 Nov 2014 (actual)
- Primary completion
- 18 Oct 2017 (actual)
- Study completion
- 2 Jul 2018 (actual)
- First posted
- 23 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Uveal melanoma is the most common primary intraocular malignancy in adults and is thought to be particularly resistant to systemic treatment, and no systemic therapy has yet been demonstrated to improve survival. Drugs commonly used to treat advanced cutaneous melanoma rarely achieve durable responses in patients with uveal melanoma. Because of the lack of effective systemic treatment options, outcomes are poor once metastatic disease occurs, and the median survival from the time of the development of distant metastatic disease is 6 to 12 months. Although it is clear that novel effective therapies are desperately needed for this disease, the development of such therapies has been hampered by the rarity of uveal melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose 1: AEB071 and BYL719 | Experimental | Drug: AEB071, Drug: BYL719AEB071, oral, 100 mg twice daily BYL719, oral, 200 mg daily |
| Dose 2: AEB071 and BYL719 | Experimental | Drug: AEB071, Drug: BYL719AEB071, oral, 200 mg twice daily BYL719, oral, 250 mg daily |
| Dose 3: AEB071 and BYL719 | Experimental | Drug: AEB071, Drug: BYL719AEB071, oral, 200 mg twice daily BYL719, oral, 300 mg daily |
| Dose 4: AEB071 and BYL719 | Experimental | Drug: AEB071, Drug: BYL719AEB071, oral, 200 mg twice daily BYL719, oral, 350 mg daily |
| Dose 5: AEB071 and BYL719 | Experimental | Drug: AEB071, Drug: BYL719AEB071, oral, 300 mg twice daily BYL719, oral, 350 mg daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AEB071Also: SotrastaurinOral, 100-400 mg twice daily A potent, oral, selective inhibitor of the classical Protein Kinase C (PKC) | Drug | Dose 1: AEB071 and BYL719, Dose 2: AEB071 and BYL719, Dose 3: AEB071 and BYL719, Dose 4: AEB071 and BYL719, Dose 5: AEB071 and BYL719 |
| BYL719Also: NVP-BYL719Oral, 200-350 mg daily An oral class I α-specific PI3K inhibitor belonging to the 2-aminothiazole class of compounds | Drug | Dose 1: AEB071 and BYL719, Dose 2: AEB071 and BYL719, Dose 3: AEB071 and BYL719, Dose 4: AEB071 and BYL719, Dose 5: AEB071 and BYL719 |
Primary outcome
Total maximum tolerated dose (in milligrams) of AEB071 in combination with BYL719
Time frame: 4 years (approximately)
Establish the maximum tolerated dose (up to 400 mg twice daily) for AEB071 and up to 350 mg daily for BYL719
6 secondary outcomes
Number of participants with adverse events
Time frame: 4 years (approximately)
Change in area under the curve (AUC) for the combination of AEB071 and BYL719
Time frame: 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
Time frame: 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
Time frame: 4 years (approximately)
Change in numerically calculated toxicity burden (0-10)
Time frame: baseline, Cycle 1 Day 8, Day 15, and Day 22, Cycle 2 and above, End of Treatment, 28 day Follow-Up visit
Mean months of overall survival
Time frame: 4 years (approximately)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Carvajal, MD principal investigator
Columbia University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AEB071 and BYL719 in people with Uveal Melanoma, run by Columbia University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total maximum tolerated dose (in milligrams) of AEB071 in combination with BYL719 (time frame: 4 years (approximately)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2023.