CC-486 (Oral Azacitidine) Bioequivalence Study in Patients With Solid Tumor or Hematologic Malignancies
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
Conditions: official terms
Breast Neoplasms - Carcinoma, Non-Small-Cell Lung - Carcinoma, Renal Cell - Glioblastoma - Hematologic Neoplasms - Hodgkin Disease - Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute - Lung Neoplasms - Lymphoma - Lymphoma, Non-Hodgkin - Multiple Myeloma - Myelodysplastic Syndromes - Neoplasms - Neoplasms, Plasma Cell - Osteosarcoma - Preleukemia - Small Cell Lung Carcinoma - Thyroid Neoplasms
Conditions: 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
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: CC-486 Type: Drug
Name: Vidaza Type: Drug
Overall Status
Recruiting
Summary
This is a Phase 1, open-label, multicenter, randomized, 2-period crossover study consisting of 2 phases: Pharmacokinetics and Extension.

The study will enroll approximately 60 subjects with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver. Approximately 8 sites in the US will participate in this study.
Detailed Description
Currently, the 150 mg tablet formulation (F8) of CC-486 is being provided to subjects in two large Phase 3 randomized placebo-controlled studies in lower-risk MDS and AML maintenance. This CC-486-CAGEN-001 study is designed to assess the bioequivalence of CC-486 when administered once daily as one 300 mg tablet (F9) relative to two 150 mg tablets (F8) in adult cancer subjects with hematologic malignancies or various tumor types excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver.

Following confirmation of eligibility during screening, subjects will be randomized to one of two dosing sequences in the pharmacokinetics (PK) phase and will have blood samples taken prior to dosing and at several time points during the 8 hours following dosing. Safety information will be collected in this phase and the PK parameters describing the levels of investigational product (IP) in circulation will be used to assess bioequivalence of the two formulations.

In the extension phase of the study, Vidaza® (Azacitidine for Injection) will be provided for ≤ 6 cycles as an opportunity for subjects who currently have limited treatment options or have failed previous therapies. It is up to the discretion of the investigator to treat the subject with Vidaza® for the diagnosed malignancy at study entry in this phase. Only safety information will be collected in this phase.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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); 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 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)

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

- 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. Have known active viral infection with human immunodeficiency virus (HIV) or active hepatitis B (HBV) or C (HCV)

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
Locations
Mayo Clinic
Scottsdale, Arizona, United States
Status: Recruiting
Scottsdale Healthcare Research Institute
Scottsdale, Arizona, United States
Status: Recruiting
Medical University of South Carolina Hollings Cancer Center
Charleston, South Carolina, United States
Status: Withdrawn
Greenville Hospital System
Greenville, South Carolina, United States
Status: Recruiting
Vanderbilt
Nashville, Tennessee, United States
Status: Recruiting
Start Date
October 2014
Completion Date
April 2016
Sponsors
Celgene Corporation
Source
Celgene Corporation
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page