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

NCT02223052 | Completed Phase 1

• 1 other identifier: CC-486-CAGEN-001
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 10

Brief Summary

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.

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

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

Outcome Measures

Primary Outcomes (16)

• Pharmacokinetics Cmax - Stage I (Bioequivalence)

  The observed maximum concentration

  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

• Pharmacokinetics Tmax - Stage I (Bioequivalence)

  The observed time to first maximum concentration

  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

• Pharmacokinetics AUC-t - Stage I (Bioequivalence)

  Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule

  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

• Pharmacokinetics AUC-infinity - Stage I (Bioequivalence)

  Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = \[AUCt + Ct/λz\]. Ct is the last quantifiable concentration

  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

• Pharmacokinetics λz (Terminal Rate) - Stage I (Bioequivalence)

  Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve

  Dosing 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 0.3.5, 4, 6, and 8 hours post-dose

• Pharmacokinetics Terminal Half-Life (t½) - Stage I (Bioequivalence)

  Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz

  Dosing 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

• Pharmacokinetics Apparent total clearance (CL/F) - Stage I (Bioequivalence)

  Apparent total clearance, calculated as Dose/AUC∞

  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

• Pharmacokinetics Apparent volume of distribution (Vd/F) - Stage I (Bioequivalence)

  Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz

  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

• Pharmacokinetics Cmax - Stage II (Food Effect Bioavailability)

  The observed maximum concentration

  PK Dosing 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.

• Pharmacokinetics Tmax - Stage II (Food Effect Bioavailability)

  The observed time to first maximum concentration

  PK Dosing 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.

• Pharmacokinetics AUC-t - Stage II (Food Effect Bioavailability)

  Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule.

  PK Dosing 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.

• Pharmacokinetics AUC-infinity - Stage II (Food Effect Bioavailability)

  Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = \[AUCt + Ct/λz\]. Ct is the last quantifiable concentration.

  PK Dosing 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.

• Pharmacokinetics λz (Terminal Rate) - Stage II (Food Effect Bioavailability)

  Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve

  PK Dosing 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.

• Pharmacokinetics Terminal Half-Life (t½) - Stage II (Food Effect Bioavailability)

  Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz

  PK Dosing 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.

• Pharmacokinetics Apparent total clearance (CL/F) - Stage II (Food Effect Bioavailability)

  Apparent total clearance, calculated as Dose/AUC∞

  PK Dosing 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.

• Pharmacokinetics Apparent volume of distribution (Vd/F) - Stage II (Food Effect Bioavailability)

  Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz

  PK Dosing 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.

Secondary Outcomes (1)

• Adverse Events (AEs)

  Up to 18 months

Study Arms (4)

CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1

EXPERIMENTAL

Two 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.

Drug: CC-486; Drug: Vidaza

CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1

EXPERIMENTAL

One 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.

Drug: CC-486; Drug: Vidaza

CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2

EXPERIMENTAL

One 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.

Drug: CC-486; Drug: Vidaza

CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2

EXPERIMENTAL

One 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.

Drug: CC-486; Drug: Vidaza

Interventions

CC-486 DRUG

Arm 1: Two 150-mg tablets of CC-486 on Day 1 and 1 x 300 mg CC-486 on Day 2 Arm 2: 1 x 300mg tablet of CC 486 on Day 1 and 2 x 150mg CC-486 on Day 2

Also known as: Oral Azacitdine

CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1; CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2; CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1; CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2

Vidaza DRUG

75mg/m\^2 IV or SC daily x 7 days every 4 weeks for ≤ 6 (four-week) cycles

Also known as: Azacitidine for Injection, AZA

CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 1; CC-486 Arm 1 (Oral Azacitidine) Dosing Sequence 2; CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 1; CC-486 Arm 2 (Oral Azacitidine) Dosing Sequence 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Age ≥ 18 years of age at the time of signing the informed consent document.
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
• Documented diagnosis of any of the following:
• Myelodysplastic Syndrome (MDS) according to the World Health Organization (WHO) 2008 classification
• Acute myeloid leukemia (AML)
• Multiple myeloma (MM), limited to those patients for whom standard curative or palliative treatments do not exist or are no longer effective
• Non-Hodgkin's lymphoma (NHL), limited to those patients for whom standard curative or palliative treatment do not exist or are no longer effective,
• Hodgkin's lymphoma (HL), limited to those patients for whom standard curative or palliative treatment do not exist or are no longer effective
• 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.
• 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).
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Have a life expectancy of ≥ 3 months.
• Have stable renal function without dialysis for at least 2 months prior to Investigational Product (IP) administration defined by:

You may not qualify if:

• Women who are pregnant or nursing (lactating).
• 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.
• Had chemotherapy or radiotherapy within 4 weeks prior to the first day of Investigational Product (IP) administration.
• Have been treated with an investigational agent within 4 weeks prior to the first day of IP administration.
• Have ongoing clinically significant adverse event(s) due to prior treatments administered as determined by the investigator.
• 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
• Have known or suspected hypersensitivity to azacitidine or any other ingredient used in the manufacturing of Azacitidine.
• 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)
• 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.
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
• Any condition that confounds the ability to interpret data from the study

Sponsors & Collaborators

• Celgene: lead

Study Sites (10)

Scottsdale Healthcare Research Institute

Scottsdale, Arizona, 85258, United States

Location

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202-268, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Greenville Hospital System

Greenville, South Carolina, 29605, United States

Location

Vanderbilt- Ingram Cancer Center

Nashville, Tennessee, 37232-6307, United States

Location

The Methodist Hospital Research Institute l

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma; Multiple Myeloma; Leukemia, Myeloid, Acute; Leukemia; Myelodysplastic Syndromes; Neoplasms; Melanoma; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Carcinoma, Renal Cell; Glioblastoma; Osteosarcoma; Sarcoma; Thyroid Neoplasms; Brain Neoplasms; Kidney Neoplasms; Lung Neoplasms; Bone Neoplasms; Testicular Neoplasms; Prostatic Neoplasms; Urinary Bladder Neoplasms; Ovarian Neoplasms; Skin Neoplasms

Interventions

cc-486; Azacitidine; Injections

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Myeloid; Bone Marrow Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Bone Diseases; Musculoskeletal Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Testicular Diseases; Gonadal Disorders; Prostatic Diseases; Urinary Bladder Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Du Lam, MD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 20, 2014
• First Posted: August 22, 2014
• Study Start: October 27, 2014
• Primary Completion: June 11, 2018
• Study Completion: December 18, 2018
• Last Updated: May 12, 2020

Record last verified: 2020-05

Locations

US (10)