A Study of CC-122 to Assess the Safety and Tolerability in Japanese Patients With Advanced Solid Tumors and Non-Hodgkin's Lymphoma (NHL)
- Registration Number
- NCT02509039
- Lead Sponsor
- Celgene
- Brief Summary
To determine the safety and tolerability of CC-122 when administered orally to adult Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL) and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
- Detailed Description
This is a phase 1, multicenter, open-label, dose-escalation study that will evaluate the safety, tolerability, (Pharmacokinetics) PK, and preliminary efficacy of CC-122 in Japanese subjects with advanced solid tumors or Non-Hodgkin's Lymphoma (NHL).
Subjects will receive ascending dose levels of CC-122 from Cycle 1 onwards to measure PK and to determine safety and tolerability.
An initial cohort of at least three subjects will be given CC-122 at a dose of 2.0 mg on an intermittent dosing schedule (5 continuous days out of 7 days per week) and 3-6 subjects will be enrolled in subsequent dose levels. Dose escalation for subsequent cohorts will proceed according to a standard dose escalation design (3+3 design) (Storer, 1989) to establish initial toxicity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
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Understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures are conducted
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20 years or older, with histological or cytological confirmation of advanced solid tumors or Non-Hodgkin's Lymphoma (NHL), including those who have progressed on standard anticancer therapy or for whom no other conventional therapy exists
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Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 for all tumors
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Subjects must have the following laboratory values:
・Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
- Hemoglobin (Hgb) ≥ 9 g/dL, drawn at least 7 days after the last RBC transfusion
- Platelets (Plt) ≥ 100 x 109/L, drawn at least 7 days after the last platelet transfusion
- Potassium within normal limits or correctable with supplements
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver tumors are present
- Serum bilirubin ≤ 1.5 x ULN; subjects with serum bilirubin >1.5 x ULN and ≤ 2 x ULN may be enrolled if agreed to by the sponsor
- Serum creatinine ≤ ULN or 24-hour clearance ≥ 50 mL/min
- Negative serum pregnancy test in females of childbearing potential as per the CC-122 Pregnancy Prevention Rist Management Plan
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Able to adhere to the study visit schedule and other protocol requirements
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Must adhere to the Pregnancy Prevention Rist Management Plan
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Subjects with primary central nervous system (CNS) malignancies or symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed
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Known acute or chronic pancreatitis
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Any peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade 2
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Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management
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Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
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Left Ventricular Ejection Fraction (LVEF) < 45% as determined by Multiple Gated Acquisition Scan (MUGA) scan or Echocardiogram (ECHO)
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Complete left bundle branch, or bifascicular block
- Congenital long QT syndrome
- Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation
- QTcF > 460 msec on screening electrocardiogram (ECG) (mean of triplicate recordings)
- Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting CC-122
- Troponin-T value >0.4 ng/mL or Brain Natriuretic Peptide (BNP) >300 pg/mL Subjects with baseline troponin-T >ULN or BNP >100 pg/mL are eligible but must and optimization of cardioprotective therapy.
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Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mmHg)
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Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting CC-122 or who have not recovered from side effects of such therapy. Luteinizing hormone-releasing hormone (LHRH) agonists will be allowed for subjects with metastatic prostate cancer
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Major surgery ≤ 2 weeks prior to starting CC-122 or still recovering from post operative side effects
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Women who are pregnant or breast feeding. Adults of reproductive potential not employing two forms of birth control as per Pregnancy Prevention Risk Management Plan (PPRMP)
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Known human immunodeficiency virus (HIV) infection
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Known acute or chronic hepatitis B or C virus infection
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Status post solid organ transplant
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Less than 100 days for subjects receiving autologous hematologic stem cell transplant (HSCT); or 6 months for subjects receiving allogeneic HSCT, or if otherwise not fully recovered from HSCT-related toxicity
a. The 6-month exclusionary period for recovery from HSCT-associated toxicity, applies regardless of whether an autologous or allogeneic transplant was performed
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Known hypersensitivity to any component of the formulation of CC-122
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Any significant medical condition (including active or controlled infection or renal disease), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
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Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
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Any condition that confounds the ability to interpret data from the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CC-122 CC-122 CC-122 is administered orally, on a 5 continuous days out of 7 days per week intermittent dosing schedule.
- Primary Outcome Measures
Name Time Method Number of Participants With Dose-Limiting Toxicities (DLTs) From first dose up to at least 28 days (Cycle 1) NCI CTCAE Version 4.03 will be used to grade adverse events. Events described below will be classified as DLTs:
* Non-hematologic AEs: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3
* Laboratory abnormalities: Suspected to be related to CC-122, commences during the DLT evaluation period, and is ≥ Grade 3
* Hematologic: Any febrile neutropenia, Grade 4 neutropenia lasting \> 7 days, Grade 4 thrombocytopenia lasting \> 24 hours or thrombocytopenia of any grade requiring platelet transfusions, Any Grade 3/4 thrombocytopenia with clinically significant bleeding
* Hepatic: Grade 4 liver function tests or Grade 3 ALT with Grade 2 or higher bilirubin will be considered a DLT, irrespective of underlying attribution. Other Grade 3 LFTs due to disease progression in the liver will not be considered DLTs
* Other adverse events: Suspected to be related to CC-122 and necessitating a dose reduction during the DLT evaluation periodMaximum Tolerated Dose (MTD) From first dose up to at least 28 days (Cycle 1) The MTD is defined as the last dose level below the non-tolerated dose (NTD) with zero or one out of six evaluable participants experiencing dose-limiting toxicities (DLTs) during the DLT evaluation period. At least 6 participants will be enrolled at the MTD/recommended phase 2 dose (RP2D).
MTD will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria Version 4.03Number of Participants With Treatment Emergent Adverse Events (TEAEs) From first dose to 28 days post last dose of investigational product (Up to approximately 92 months) An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria version 4.03
Pharmacokinetic Parameters of CC-122: AUC0-t 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Area under the plasma concentration time-curve up to the last measurable concentration (AUC0-t)
Pharmacokinetic Parameters of CC-122: AUCtau 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Area under the plasma concentration time-curve during a dosing interval (AUCtau)
Pharmacokinetic Parameters of CC-122: Cmax 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Peak (maximum) plasma concentration (Cmax)
Pharmacokinetic Parameters of CC-122: Tmax 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Time to maximum plasma concentration (Tmax)
Pharmacokinetic Parameters of CC-122: t1/2 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Terminal half-life of CC-122 (t1/2)
Pharmacokinetic Parameters of CC-122: CL/F 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Apparent clearance (CL/F)
Pharmacokinetic Parameters of CC-122: Vz/F 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Apparent volume of distribution (Vz/F)
Accumulation Index of CC-122 0, 0.5, 0.75, 1, 1.5, 3, 5, 8 and 24 hours post dose of Cycle 1 Day 1, 10, 11 or 12 (Cycle = 28 Days) Accumulation Index defined as AUCtau (Cycle 1 Day 10, 11 or 12)/AUCtau (Cycle 1 Day 1)
- Secondary Outcome Measures
Name Time Method Best Overall Response (BOR) From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days) BOR by investigator is defined according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma for NHL patients and Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for solid tumors patients. For NHL, complete remission (CR)=disappearance of all evidence of disease. Partial response (PR)=regression of measurable disease and no new sites. Stable disease (SD)=failure to attain CR/PR or PD. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir. For solid tumors, complete response (CR)=disappearance of all target and non-target lesions and no new lesions. PR=at least a 30% decrease in the sum of diameters of target lesions and no new lesions. SD=neither sufficient shrinkage to qualify for PR or increase to qualify for PD. PD=at least 20% increase in the sum of diameters of target lesions from nadir.
Duration of Response (DoR) From first dose until objectively documented progression (Up to 92 Months) at Day 15 of Cycle 2, 4, 6, and every 3 cycles thereafter (Cycle = 28 Days) DoR for NHL patients is defined as the time from the date when complete response (CR) or partial response (PR), whichever is first recorded are met, until the date when disease progression (PD) is first objectively documented, or the date of the last adequate tumor assessment when no disease progression is documented throughout the study according to International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR=disappearance of all evidence of disease. PR=regression of measurable disease and no new sites. Progressive disease (PD)=any new lesion or increase by \>=50% of previously sites from nadir.
Trial Locations
- Locations (3)
Local Institution - 003
🇯🇵Chikusa-ku, Japan
Local Institution - 001
🇯🇵Kashiwa, Japan
Local Institution - 002
🇯🇵Koto-ku, Tokyo, Japan