Malignant MelanomaPhase 1NCT02935790

Selective HDAC6 Inhibitor ACY-241 in Combination With Ipilimumab and Nivolumab

A Phase 1 study testing ACY-241, nivolumab and ipilimumab in people with Malignant Melanoma, run by Celgene at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Malignant Melanoma
What is being tested?: ACY-241, nivolumab and ipilimumab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 1 siteUnited States
Study dates: 30 Sep 2016to 7 Apr 2017
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

Patients must have signed and dated an Institutional Review Board/Independent Ethics Committee -approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care
Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
All patients must be either Stage IIIb/c or Stage IV according to the American Joint Committee on Cancer (AJCC) (7th edition) and have histologically-confirmed melanoma that is felt to be surgically unresectable in order to be eligible. Please refer to the AJCC Cancer Staging Manual, 7th edition for a description of tumor, lymph node, metastasis and staging.
All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed; mucosal melanomas are eligible.
Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical).
-Exceptions: Surgery for melanoma and/or postresection brain radiotherapy (RT) if central nervous system (CNS) metastases and/or prior treatment with adjuvant interferon (IFN) (as described in Exclusion Criterion 2).

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All patients must have their disease status documented by a complete physical examination and imaging studies within 4 weeks prior to the first dose of study drug. Imaging studies must include computerized tomography (CT) scan of neck, chest, abdomen, pelvis, and all known sites of resected disease in the setting of Stage IIIb/c or Stage IV disease, and brain magnetic resonance imaging ([MRI], brain CT allowable if MRI is contraindicated).
The complete set of baseline radiographic images must be available before treatment initiation.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Tumor tissue from the resected site of disease must be provided for biomarker analyses
Prior treated CNS metastases must be without MRI evidence of recurrence for at least 4 weeks after treatment. Patients must be off immunosuppressive doses of systemic steroids (≥ 10 mg/day prednisone or equivalent) for at least 14 days prior to study drug administration, and must have returned to neurologic baseline status postoperatively.
The 4-week period of stability is measured after the completion of the neurologic interventions (ie, surgery and/or radiation).
In addition to neurosurgery to treat CNS metastases, adjuvant radiation after the resection of CNS metastasis is allowed. Immunosuppressive doses of systemic steroids (doses ≥ 10 mg/day prednisone or equivalent) must be discontinued at least 14 days before study drug administration.
Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration.
All baseline laboratory requirements will be assessed and should be obtained within 14 days of first dose of study drug. Screening laboratory values must meet the following criteria:
White blood cells ≥ 2000/µL
Neutrophils ≥ 1500/µL
Platelets ≥ 100 × 10³/µL
Hemoglobin ≥ 9.0 g/dL
Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula)
Patient Re-enrollment: This study permits the re-enrollment of a patient that has discontinued the study as a screen failure (ie, patient has not been dosed/has not been treated). If re-enrolled, the patient must be re-consented.
Males and females ≥ 18 years of age.
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin hormone) within 24 hours prior to the start of study drug.
Women must not be breastfeeding.
Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle). The half-lives of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. Given the blinded nature of this study, WOCBP should therefore use an adequate method to avoid pregnancy for a total of 23 weeks posttreatment completion.
Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half lives of the study drug(s) plus 90 days (duration of sperm turnover). The half-lives of nivolumab and ipilimumab are up to 25 days and 18 days, respectively. Given the blinded nature of this study, men should therefore use an adequate method of contraception for a total of 31 weeks posttreatment completion.
Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section.
Investigators shall counsel WOCBP and male patients who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male patients who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly.

Who cannot join

Patients with carcinomatosis meningitis or a history of ocular/uveal melanoma are excluded.
Patients with previous nonmelanoma malignancies are excluded unless a complete resection or remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include, but are not limited to, nonmelanoma skin cancers, in situ bladder cancer, in situ gastric cancer or gastrointestinal stromal tumor, in situ colon cancers, in situ cervical cancers/dysplasia, or breast carcinoma in situ).
Patients with active, known, or suspected autoimmune disease. Patients with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the Principal Investigator be consulted prior to signing informed consent.
Patients with a condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
Prior therapy for melanoma with the following exceptions which are allowed: 1) surgery for the melanoma lesion(s), 2) adjuvant RT after neurosurgical resection for CNS lesions, and 3) prior adjuvant IFN (see qualifier below). Specifically, patients who received prior therapy with anti-PD-1, anti PD L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell costimulation or checkpoint pathways) are not eligible.
Prior treatment with adjuvant IFN is allowed if completed ≥ 3 months prior to treatment.

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Treatment directed against the melanoma (eg, chemotherapy, targeted agents, biotherapy, limb perfusion) that is administered after a prior complete resection other than adjuvant radiation after neurosurgical resection and IFN for resected melanoma.
Previous therapy with histone deacetylase inhibitor.
Any of the following laboratory abnormalities:
ANC < 1,500/µL
Platelet count < 100,000/µL
Hematologic growth factors are not allowed at screening or during the first cycle of treatment
Hemoglobin < 9 g/dL (< 5.5 mmol/L; previous red blood cell transfusion is permitted)
Creatinine > 1.5 × ULN
AST or ALT > 2.5 × ULN. For patients with liver metastasis, AST or ALT > 5 × ULN
Serum total bilirubin > 1.5 mg/dL or > 3 × ULN for patients with hereditary benign hyperbilirubinemia
Corrected QT interval (QTc) using Fridericia's formula value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).
Congestive heart failure (New York Heart Association Class III or IV), myocardial infarction within 12 months before starting study treatment, or unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy.
Any positive test result for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome.
History of Grade ≥ 3 allergy to human monoclonal antibodies.
Prisoners or patients who are involuntarily incarcerated.
Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Pregnant or nursing women.
Psychological, familial, sociological, or geographical conditions that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

NYU Langone Medical Center
New York, New York, 10016

Other trials in United States

About this study

Official title: A Phase 1b Study of the Selective HDAC6 Inhibitor ACY-241 in Combination With Ipilimumab and Nivolumab in Patients With Unresectable Stage III or Stage IV Melanoma

Read the detailed description

This is a Phase 1b, open-label, dose-escalation cohort study. The study will consist of a dose escalation assessment of the safety and tolerability of ACY-241 administered concurrently in combination with ipilimumab and nivolumab to patients with advanced melanoma. Treatment will be divided into induction and maintenance phases.

Determine the safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of ACY-241 in combination with ipilimumab at 1 mg/kg and nivolumab at 3 mg/kg every 3 weeks for 4 doses each during a 12-week induction period, then administered with nivolumab at a flat dose of 240 mg every 2 weeks in maintenance for up to 1 year in patients with unresectable Stage III/Stage IV melanoma.

It is anticipated that this clinical study will enable selection of the RP2D and dose schedule of this 3-drug combination for further clinical testing. The trial will include an assessment of the pharmacodynamic activity of ACY-241.

Conditions: Malignant Melanoma
Being tested: ACY-241, nivolumab, ipilimumab
Keywords: unresectable, melanoma
Medical subject headings: Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ACY-241Drug
Also called HDAC6 Inhibitor
tablet
nivolumabDrug
Also called OPDIVO
infusion
ipilimumabDrug
Also called YERVOY
infusion

Study groups in NCT02935790
Study group	Role	What they receive
ACY-241 combo with Ipi and Nivo	Experimental	ACY-241 in Combination with Ipilimumab and Nivolumab Receives: Drug: ACY-241; Drug: nivolumab; Drug: ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Dose Limiting Toxicities defining the MTD
Measured: 12 months

Secondary outcomes (4)

Percentage of Patients with ORR based on RECIST 1.1 change from baseline by CT or MRI measurements
Measured: 12 months
Percentage of Patients with ORR based on irRC change from baseline by CT or MRI measurements
Measured: 12 months
Maximum observed concentration (Cmax) of ACY-241 administered in combination with ipilimumab and nivolumab
Measured: 12 months
trough concentrations of ACY-241 administered in combination with ipilimumab and nivolumab
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 20167 Apr 2017

First posted18 Oct 2016 (estimated)
Study start30 Sep 2016
Primary completion7 Apr 2017
Study completion7 Apr 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Malignant MelanomaStudies of the same condition, open and under way.
More trials run by CelgeneThe 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02935790
Sponsor's protocol ID: ACE-ST-204
Status last verified: Aug 2017
First submitted: 3 May 2016
Last updated: 24 Aug 2017
Results posted: No
Data monitoring committee: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b Study of the Selective HDAC6 Inhibitor ACY-241 in Combination With Ipilimumab and Nivolumab in Patients With Unresectable Stage III or Stage IV Melanoma
ClinicalTrials.gov ID: NCT02935790
Acronym / sponsor ID: ACE-ST-204
Conditions: Malignant Melanoma
Keywords: unresectable, melanoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 1 participants (actual)
Lead sponsor: CelgeneIndustry (pharma, biotech, devices)
Collaborators: Syneos Health, ApoCell, Inc., Celerion, NYU Langone Health
Study start: 30 Sep 2016 (actual)
Primary completion: 7 Apr 2017 (actual)
Study completion: 7 Apr 2017 (actual)
First posted: 18 Oct 2016 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ACY-241 combo with Ipi and Nivo	Experimental	Drug: ACY-241, Drug: nivolumab, Drug: ipilimumabACY-241 in Combination with Ipilimumab and Nivolumab

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (28 listed)

Patients must have signed and dated an Institutional Review Board/Independent Ethics Committee -approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care
Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
All patients must be either Stage IIIb/c or Stage IV according to the American Joint Committee on Cancer (AJCC) (7th edition) and have histologically-confirmed melanoma that is felt to be surgically unresectable in order to be eligible. Please refer to the AJCC Cancer Staging Manual, 7th edition for a description of tumor, lymph node, metastasis and staging.
-Exceptions: Surgery for melanoma and/or postresection brain radiotherapy (RT) if central nervous system (CNS) metastases and/or prior treatment with adjuvant interferon (IFN) (as described in Exclusion Criterion 2).
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Key exclusion criteria (26 listed)

Patients with carcinomatosis meningitis or a history of ocular/uveal melanoma are excluded.
Patients with previous nonmelanoma malignancies are excluded unless a complete resection or remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include, but are not limited to, nonmelanoma skin cancers, in situ bladder cancer, in situ gastric cancer or gastrointestinal stromal tumor, in situ colon cancers, in situ cervical cancers/dysplasia, or breast carcinoma in situ).
Patients with active, known, or suspected autoimmune disease. Patients with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the Principal Investigator be consulted prior to signing informed consent.
Patients with a condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
Prior therapy for melanoma with the following exceptions which are allowed: 1) surgery for the melanoma lesion(s), 2) adjuvant RT after neurosurgical resection for CNS lesions, and 3) prior adjuvant IFN (see qualifier below). Specifically, patients who received prior therapy with anti-PD-1, anti PD L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell costimulation or checkpoint pathways) are not eligible.

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
ACY-241Also: HDAC6 Inhibitortablet	Drug	ACY-241 combo with Ipi and Nivo
nivolumabAlso: OPDIVOinfusion	Drug	ACY-241 combo with Ipi and Nivo
ipilimumabAlso: YERVOYinfusion	Drug	ACY-241 combo with Ipi and Nivo

Primary outcome

Number of Dose Limiting Toxicities defining the MTD
Time frame: 12 months

4 secondary outcomes

Percentage of Patients with ORR based on RECIST 1.1 change from baseline by CT or MRI measurements
Time frame: 12 months
Percentage of Patients with ORR based on irRC change from baseline by CT or MRI measurements
Time frame: 12 months
Maximum observed concentration (Cmax) of ACY-241 administered in combination with ipilimumab and nivolumab
Time frame: 12 months
trough concentrations of ACY-241 administered in combination with ipilimumab and nivolumab
Time frame: 12 months

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 24 Aug 2017.
Individual participant dataSharing planned: Undecided

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RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
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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.

Jeffrey S Weber principal investigator

Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center

Elizabeth Buchbinder principal investigator

Dana-Farber Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ACY-241, nivolumab and ipilimumab in people with Malignant Melanoma, run by Celgene at 1 site 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 28 inclusion and 26 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 24 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Number of Dose Limiting Toxicities defining the MTD (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02935790.

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 24 Aug 2017.