Clinical Trials /

Selective HDAC6 Inhibitor ACY 241 in Combination With Nivolumab in Patients With Unresectable Non Small Cell Lung Cancer

NCT02635061

Description:

Determine the safety, tolerability, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of ACY 241 in combination with nivolumab.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Selective HDAC6 Inhibitor ACY 241 in Combination With Nivolumab in Patients With Unresectable Non Small Cell Lung Cancer
  • Official Title: A Phase 1b Study of the Selective HDAC6 Inhibitor ACY 241 in Combination With Nivolumab in Patients With Unresectable Non Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: ACE-ST-203
  • NCT ID: NCT02635061

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
ACY-241ACY-241 in combination with nivolumab and ipilimumab
NivolumabOpdivoACY-241 in combination with nivolumab and ipilimumab

Purpose

Determine the safety, tolerability, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of ACY 241 in combination with nivolumab.

Trial Arms

NameTypeDescriptionInterventions
ACY-241 in combination with nivolumab and ipilimumabExperimental
  • ACY-241
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Must be able to understand and voluntarily sign an informed consent form (ICF).

          2. Must be ≥ 18 years of age at the time of signing the ICF.

          3. Must be able to adhere to the study visit schedule and other protocol requirements.

          4. Patients must have histologically confirmed unresectable NSCLC for which nivolumab is
             clinically appropriate. Patients must have had one line of prior therapy and have
             progressed or have discontinued due to toxicity.

          5. Measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1
             (RECIST 1.1) and Immune related Response Criteria (irRC).

          6. Life expectancy > 12 weeks.

          7. Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1,
             or 2.

          8. Willingness to have pre treatment and on treatment tumor biopsies.

          9. Patients with the potential for pregnancy or impregnating their partner must agree to
             follow acceptable birth control methods to avoid conception. Female patients of
             childbearing potential must agree to use adequate contraceptive measures until 3
             months after the last study drug is taken. Females of childbearing potential must
             have a negative pregnancy test. It is not known if the antideacetylase activity of
             this experimental drug may be harmful to the developing fetus or nursing infant.

         10. Male patients should be willing to use barrier contraceptive (ie, condoms) until 3
             months after last study drug is taken.

        Exclusion Criteria:

          1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the patient from giving informed consent.

          2. Any serious concurrent medical conditions, laboratory abnormality, or psychiatric
             illness that might make the patient nonevaluable, put the patient's safety at risk,
             or prevent the patient from following the study requirements.

          3. Pregnant or lactating females.

          4. Patients with uncontrolled brain metastases. Existing brain metastases must have been
             previously treated and currently stable.

          5. Patients who have had chemotherapy within 14 days before entering the study or those
             who have not recovered from AEs to ≤ Grade 1 due to agents administered more than 14
             days earlier.

          6. Previous therapy with histone deacetylase (HDAC) inhibitor and/or anti PD 1, anti PD
             L1, or anti CTLA4 immunotherapy.

          7. 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 × upper limit of normal (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

          8. Corrected QT interval (QTc) using Fridericia's formula (QTcF) 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).

          9. 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.

         10. Patients with chronic autoimmune disease(s) requiring systemic immunosuppression.

         11. Positive human immunodeficiency virus, hepatitis B virus, and hepatitis C virus
             infection.

         12. Patients who received any of the following within the 14 days before initiating study
             treatment: major surgery, radiation therapy, and/or systemic therapy (standard or an
             investigational or biological anticancer agent).

         13. Current enrollment in another clinical study involving treatment and/or is receiving
             an investigational agent for any reason, or use of any investigational agents within
             14 days of initiating study treatment.

         14. Incidence of gastrointestinal disease that may significantly alter the absorption of
             ACY 241.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:one to two years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:preliminary antitumor activity of ACY 241 in combination with nivolumab
Time Frame:one to two years
Safety Issue:
Description:
Measure:Maximum Plasma Concentration [Cmax] of ACY 241 in combination with nivolumab on biomarkers in peripheral blood and tumor tissue
Time Frame:one to two years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Last Updated

April 5, 2017