Clinical Trials /

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

NCT02223052

Description:

This is a Phase 1, open-label, multicenter, randomized, 2-stage crossover study consisting of 2 phases: Stage I - Pharmacokinetics (Bioequivalence), with an Extension Stage II - Pharmacokinetics (Food Effect) with an Extension This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the US and 2 in Canada will participate in this study.

Related Conditions:
  • Acute Myeloid Leukemia
  • Hodgkin Lymphoma
  • Malignant Solid Tumor
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies
  • Official Title: A Phase 1, Open-label, Multicenter, Randomized, 2-Period, Crossover Study to Evaluate the Bioequivalence and Food Effect Bioavailability of CC-486 (Oral Azacitidine) Tablets in Adult Cancer Subjects

Clinical Trial IDs

  • ORG STUDY ID: CC-486-CAGEN-001
  • NCT ID: NCT02223052

Conditions

  • Hematological Neoplasms
  • Non-Hodgkin's Lymphoma
  • Hodgkin's Lymphoma
  • Lymphoma
  • Multiple Myeloma
  • Acute Myeloid Leukemia
  • Leukemia
  • Myelodysplastic Syndromes
  • Neoplasms
  • Melanoma
  • Breast Cancer
  • Metastatic Breast Cancer
  • Non-Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Renal Cell Carcinoma
  • Glioblastoma Multiforme
  • Osteosarcoma
  • Sarcoma
  • Thyroid Cancer
  • Genitourinary

Interventions

DrugSynonymsArms
CC-486Oral AzacitdineCC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1
VidazaAzacitidine for Injection, AZACC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1

Purpose

This is a Phase 1, open-label, multicenter, randomized, 2-stage crossover study consisting of 2 phases: Stage I - Pharmacokinetics (Bioequivalence), with an Extension Stage II - Pharmacokinetics (Food Effect) with an Extension This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the US and 2 in Canada will participate in this study.

Detailed Description

      Stage I - Pharmacokinetics (Bioequivalence)

      Subjects will be randomized to receive CC-486 300 mg orally on each of the two
      pharmacokinetic (PK) study days based on the dosing sequences they are randomized to:

      Dosing Sequence 1: 2x150 mg tablets followed by 1x30 mg tablet. Dosing Sequence 2: 1x300 mg
      tablet followed by 2x150 mg tablets. Each dose will be administered in the clinic at least 48
      hours apart between PK dosing day 1 and PK dosing day 2 over a period no longer than 10 days
      under fasted conditions.

      Stage II - Pharmacokinetics (Food Effect)

      Subjects will be randomized to receive CC-486 300 mg orally on each of the two PK study days
      based on the dosing sequences they are randomized to:

      Dosing Sequence 1: 1x300 mg tablet under fasted condition followed by 1x300 mg tablet under
      fed condition.

      Dosing Sequence 2: 1x300 mg tablet under fed condition followed by 1x300 mg tablet under
      fasted condition.

      Each dose will be administered in the clinic at least 48 hours apart between PK dosing day 1
      and PK dosing day 2 over a period no longer than 10 days. The sponsor will generate the
      randomization scheme and assign subjects upon enrollment to the appropriate sequence for
      dosing:

      Fasted condition: following an overnight fast of at least 10 hours, subjects will ingest oral
      Azacitidine with 240 mL of room temperature water. Subjects must fast for a minimum of 4
      hours following oral Azacitidine administration. Subjects may drink water as desired, except
      for 1 hour before and 1 hour after oral Azacitidine administration.

      Fed condition: following an overnight fast of at least 10 hours and following the performance
      of all required pre-dose assessments, subjects randomized to receive test medication in a fed
      state will begin ingesting a breakfast meal 30 (±5) minutes prior to the planned
      administration of oral Azacitidine. They will continue the entire meal within 20 to 25
      minutes (no less than 20 minutes) from the time the meal is served. Subjects will then ingest
      oral Azacitidine with 240 mL of room temperature water. Subjects must fast a minimum of 4
      hours following oral Azacitidine administration. Subjects may drink water as desired, except
      for 1 hour before and 1 hour after administration of oral Azacitidine.

      Extension Phase (for subjects who have completed PK Stage I or Stage II) Subjects continuing
      beyond the pharmacokinetics phase (Stage I or Stage II) will enter the extension phase of the
      study at the discretion of the investigator to receive < 6 (four-week) cycles of Vidaza 75
      mg/m2 IV or SC daily for 7 days in the clinic and repeat every 4 weeks per prescribed label
      at the discretion of the investigator for ≤ 6 (four-week) cycles.
    

Trial Arms

NameTypeDescriptionInterventions
CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1ExperimentalTwo 150-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of CC-486 on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.
  • CC-486
  • Vidaza
CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1ExperimentalOne 300-mg tablet of oral CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.
  • CC-486
  • Vidaza
CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2ExperimentalOne 300-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by two 150-mg tablets on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.
  • CC-486
  • Vidaza
CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2ExperimentalOne 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 1, followed by one tablet of 300-mg oral CC-486 under fasted conditions on PK dosing Day 2; if PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine of Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.
  • CC-486
  • Vidaza

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must satisfy the following criteria to be enrolled in the study:

               1. Age ≥ 18 years of age at the time of signing the informed consent document.

               2. Understand and voluntarily sign an informed consent document prior to any study
                  related assessments/procedures are conducted.

               3. Documented diagnosis of any of the following:

                    1. Myelodysplastic Syndrome (MDS) according to the World Health Organization
                       (WHO) 2008 classification

                    2. Acute myeloid leukemia (AML)

                    3. Multiple myeloma (MM), limited to those patients for whom standard curative
                       or palliative treatments do not exist or are no longer effective

                    4. Non-Hodgkin's lymphoma (NHL), limited to those patients for whom standard
                       curative or palliative treatment do not exist or are no longer effective,

                    5. Hodgkin's lymphoma (HL), limited to those patients for whom standard
                       curative or palliative treatment do not exist or are no longer effective

                    6. Metastatic or inoperable solid tumors* (except gastrointestinal tumors or
                       tumors that originated or metastasized to the liver) for which no standard
                       treatment exists, or have progressed or recurred following prior therapy.

                         -  Subjects must not be eligible for therapy of higher curative potential
                            where an alternative treatment has been shown to prolong survival in an
                            analogous population.

               4. Patients with a history of treated brain metastases should be clinically stable
                  for ≥ 4 weeks prior to signing the informed consent. Glucocorticoid therapy for
                  central nervous system (CNS) edema is permitted if ≤ 20 mg of prednisolone (or
                  equivalent).

               5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

               6. Have a life expectancy of ≥ 3 months.

               7. Have stable renal function without dialysis for at least 2 months prior to
                  Investigational Product (IP) administration defined by:

                    1. Serum creatinine < 2.5 x the upper limit of normal (ULN)

                    2. An average calculated creatinine clearance > 30 mL/min/1.73 m^2

               8. Have organ and marrow function at the screening and pre-dose visits as defined
                  by:

                    1. Hemoglobin ≥ 8 g/dL

                    2. Absolute neutrophil count (ANC) ≥ 0.75 x 10^3/uL without treatment with a
                       myeloid growth factor within 3 days prior to first dose of IP

                    3. Platelets ≥ 30 x 10^3/uL

                    4. Total bilirubin ≤ 1.5 x Upper Limits of Normal (ULN)

                    5. Aspartate aminotransferase (AST) ≤ 2 x ULN

                    6. Alanine aminotransferase (ALT) ≤ 2 x ULN

               9. Have a 12-lead Electrocardiogram (ECG) that is not clinically significant at
                  screening, as determined by the investigator

              10. Females of childbearing potential (FCBP) may participate, providing the subject
                  meets the following conditions:

                    -  Agree to use at least two effective contraceptive methods (oral, injectable,
                       or implantable hormonal contraceptive; tubal ligation; intra-uterine device;
                       barrier contraceptive with spermicide; or vasectomized partner) or agree to
                       practice true abstinence throughout the study, and for 3 months following
                       the last dose of IP; and

                    -  Negative serum pregnancy test at screening (sensitivity of at least 25
                       mIU/mL); (Note that the screening serum pregnancy test can be used as the
                       test prior to starting IP in the pharmacokinetics phase if it is performed
                       within the 72-hour timeframe), and

                    -  Negative serum or urine pregnancy test (investigator's discretion;
                       sensitivity of at least 25 mIU/mL) within 72 hours prior to starting IP in
                       the extension phase. (Note: subjects must have negative serum or urine
                       pregnancy test prior to dosing on Day 1 of each treatment cycle in the
                       extension phase.)

              11. Male subjects must:

                  a. Practice true abstinence* or agree to the use of at least two
                  physician-approved contraceptive methods throughout the course of the study and
                  should avoid fathering a child during the course of the study for at least 3
                  months following the last dose of IP.

                  * True abstinence is acceptable when this is in line with the preferred and usual
                  lifestyle of the patient. [Periodic abstinence (e.g., calendar, ovulation,
                  symptothermal, post-ovulation methods) and withdrawal are not acceptable methods
                  of contraception].

              12. Able to adhere to the study visit schedule and other protocol requirements.

        Exclusion Criteria:

          1. Women who are pregnant or nursing (lactating).

          2. Gastrointestinal tumors, tumors that have originated or metastasized to the liver, or
             other tumors known to interfere with the absorption, distribution, metabolism, or
             excretion of drugs.

          3. Had chemotherapy or radiotherapy within 4 weeks prior to the first day of
             Investigational Product (IP) administration.

          4. Have been treated with an investigational agent within 4 weeks prior to the first day
             of IP administration.

          5. Have ongoing clinically significant adverse event(s) due to prior treatments
             administered as determined by the investigator.

          6. Significant active cardiac disease within the previous 6 months, including:

               -  New York Heart Association (NYHA) class IV congestive heart failure

               -  Significant cardiac arrhythmia or unstable angina or angina requiring surgical or
                  medical intervention; and/or

               -  Myocardial infarction

          7. Have known or suspected hypersensitivity to azacitidine or any other ingredient used
             in the manufacturing of Azacitidine.

          8. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing
             signs/symptoms related to the infection without improvement despite appropriate
             antibiotics, antiviral therapy, and/or other treatment)

          9. History of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis),
             celiac disease, prior gastrectomy, gastric bypass, upper bowel removal, or any other
             gastrointestinal disorder or defect that would interfere with the absorption of the
             study drug and/or predispose the subject to an increased risk of gastrointestinal
             toxicity.

         10. Any significant medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from participating in the study.

         11. Any condition including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study

         12. Any condition that confounds the ability to interpret data from the study

         13. Impaired ability to swallow oral medication

         14. Any condition that confounds the ability to interpret data from the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pharmacokinetics Cmax - Stage I (Bioequivalence)
Time Frame:Day 1 and PK Dosing Day 2 prior to each dose administration of IP (CC-486), known as pre-dose, and over the 8-hour period following each dose administration of IP (CC-486) at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5, 4, 6, and 8 hours post-dose
Safety Issue:
Description:The observed maximum concentration

Secondary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:Up to 18 months
Safety Issue:
Description:Adverse Event (AE) is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE.

Details

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

Trial Keywords

  • CC-486
  • Oral Azacitidine
  • Soli Tumor Malignancy
  • Hematological Malignancy
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Neoplasms
  • Melanoma
  • Breast Cancer
  • Metastatic Breast Cancer
  • Non-Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Renal Cell Carcinoma
  • Glioblastoma Multiforme
  • Brain Cancer
  • Kidney Cancer
  • Lung cancer
  • Blood Cancer
  • Thyroid Cancer
  • Bone Cancer
  • Bone Metastasis
  • Testicular Cancer
  • Prostate Cancer
  • Bladder Cancer
  • Ovarian Cancer
  • Skin Cancer
  • Cancer general
  • Survival
  • Chemotherapy
  • Targeted Therapy
  • Genitourinary
  • MM
  • MDS
  • AML
  • NHL
  • HL
  • MBC
  • NSCLC
  • SCLC
  • GBM

Last Updated

July 21, 2017