Multiple MyelomaPhase 1/2NCT01177397

Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma

A Phase 1/2 study testing CC-223 in people with Multiple Myeloma and Diffuse Large B-Cell Lymphoma, run by Celgene at 16 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The main purpose of this first human study with CC-223 is to assess the safety and action of a new class of experimental drug (dual mTOR inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor type for later-stage clinical trials. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Multiple Myeloma, Diffuse Large B-Cell Lymphoma, Glioblastoma Multiforme
What is being tested?: CC-223
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 226 participants
Where: 16 sitesin 4 countries
Study dates: 20 Jul 2010to 9 Dec 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically-confirmed advanced solid tumor, Non-Hodgkin Lymphoma or multiple myeloma
Patients have not tolerated or progressed on standard therapy, and no further standard therapy is available
Archival and screening tumor biopsy
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (solid tumors), 0-2 (hematologic malignancy)
Adequate organ function

Who cannot join

Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy. Subjects must have recovered from any effects of recent radiotherapy that might confound the safety evaluation of study drug
Symptomatic brain metastases (prior Rx and stable metastases are OK)
Acute or chronic liver or renal disease or pancreatitis
Diarrhea ≥ Grade 2, impaired GI absorption
Impaired cardiac function
Diabetes requiring Rx, glucose >126 mg/dL, HbA1c ≥6.5%

Show all 12Show fewer

Peripheral neuropathy ≥ Grade 2
Pulmonary fibrosis
Known HIV infection
Known chronic hepatitis B or C virus (HBV/HCV) infection, unless comorbidity in subjects with HCC
Pregnant, inadequate contraception
Most concurrent second malignancies

Trial locations and contacts

16 sites in 4 countries.

Country

City, postcode or hospital

16 sites in 4 countries

United States10 sites

Billings Clinic
Billings, Montana, 59102
Mary Crowley Medical Research Center
Dallas, Texas, 75201
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UCLA Neuro-Oncology Program
Los Angeles, California, 90095
Sarah Cannon Research Institute Drug Development Unit
Nashville, Tennessee, 37203
NYU Cancer Institute - Bellevue Hospital
New York, New York, 10016
Mayo Clinic Cancer Clinical Studies Unit
Rochester, Minnesota, 55905
University of California, San Francisco Hellen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Moffitt Cancer Center
Tampa, Florida, 33612

Other trials in United States

France2 sites

Institut Claudius Regaud
Toulouse, 31052
Institut Gustave Roussy Faculte de Medecine Paris Sud Service de pneumologie
Villejuif, 94800

Other trials in France

Spain2 sites

Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Virgen Del Rocio
Seville, 41013

Other trials in Spain

United Kingdom2 sites

Sarah Cannon Research Institute UK
London, W1G 6AD
UCL Cancer Institute
London, WC1E 6BT

Other trials in United Kingdom

About this study

Official title: A Phase 1/2, Multi-Center, Open-Label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTOR Kinase Inhibitor CC-223 Administered Orally to Subjects With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Multiple Myeloma

Read the detailed description

Initially, patients will be treated with oral CC-223 for one month. During this time, various tests (involving blood and urine collections, ECGs, etc) will be performed. Those whose tumors stabilize or regress may continue receiving treatment for as long as they benefit from CC-223. Different dose levels of CC-223 will be tested in a dose-rising study design.

Conditions: Multiple Myeloma, Diffuse Large B-Cell Lymphoma, Glioblastoma Multiforme, Hepatocellular Carcinoma, Non-Small Cell Lung Cancer, Neuroendocrine Tumors of Non-Pancreatic Origin
Being tested: CC-223
Keywords: Advanced solid malignant neoplasms,Non-Hodgkin Lymphoma,, Multiple Myeloma
Medical subject headings: Multiple Myeloma, Lymphoma, Large B-Cell, Diffuse, Glioblastoma, Carcinoma, Hepatocellular, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CC-223Drug
Part A: (closed to enrollment) Dose level starts with 7.5mg daily taken by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose level is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity). Part B: (closed to enrollment) Optimal dose is administered in 28 day cycles until disease progression.

Study groups in NCT01177397
Study group	Role	What they receive
CC-223	Experimental	All patients will receive CC-223, but serial patient groups will receive different dose levels in Phase 1. The number of groups will be determined by the number of dose levels required to establish dose-limiting toxicity. Receives: Drug: CC-223

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With Dose-limiting Toxicities
A dose-limiting toxicity was defined as: - ≥ Grade 3 (per Common Terminology Criteria for Adverse Events [CTCAE] Version 4) clinically relevant adverse event (AE) or laboratory abnormality suspected to be related to CC-223 that commenced within 30 days of first dose, except alopecia, Grade 3 rash of the acneiform or maculopapular type for < 5 days, Grade 3 diarrhea or vomiting lasting < 72 hours, repeated occurrence of Grade 3 hyperuricaemia in subjects with Grade 3 hyperuricemia at baseline, hyperglycemia, hematologic and liver function test (LFT) abnormalities due to disease progression. - Grade 2 fasting hyperglycemia lasting > 14 days or ≥ Grade 3 lasting > 4 days despite optimal medical treatment. - Hematological toxicities including febrile neutropenia, Grade 4 neutropenia or thrombocytopenia for > 7 days, or Grade 3/4 thrombocytopenia with clinically significant bleeding. - Grade 4 LTFs - AE suspected to be CC-223 related necessitating dose reduction during cycle 1.
Measured: From first dose up to 30 days after first dose
Maximum Observed Plasma Concentration (Cmax) of CC-223
Cmax is defined as the maximum observed concentration (in plasma), obtained directly from the observed concentration versus time data. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Time to Maximum Concentration (Tmax) of CC-223
Tmax is defined as the time to Cmax, obtained directly from the observed concentration versus time data. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for CC-223
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Measured: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for CC-223
AUC0-24 is defined as the area under the concentration-time curve from Time 0 to 24 hours after a dose. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Measured: 0 to 24 hours post-dose on Day -1 and Day 15
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) For CC-223
AUCinf is defined as the area under the concentration-time curve from Time 0 extrapolated to infinity. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. AUCinf was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Part A: Terminal Elimination Phase Half-Life (T1/2) of CC-223
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. T1/2 was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Measured: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose
Apparent Total Body Clearance (CL/F) of CC-223
CL/F is defined as the apparent total body clearance when dosed orally, calculated as Dose/AUCinf. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Apparent Volume of Distribution (Vz/F) of CC-223
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. VZ/F was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Measured: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose
Part B: Progression Free Survival (PFS) Rate at 6 Months for GBM Participants
Progression free survival rate of GBM participants at 6 months is defined as the percentage of participants without progressive disease per Evaluation Criteria in Solid Tumors (RECIST) 1.1 6 months after starting study treatment. Progressive disease is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: From first dose to 6 months

Secondary outcomes (14)

Part A: Percent Change From Baseline in Levels of Phosphorylated Ribosomal Protein S6 (pS6RP) in Stimulated B Cells
Phosphorylated S6RP is a biomarker for inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Phosphorylated S6RP was measured in stimulated B cells via flow cytometry. The raw measurements were expressed as median fluorescence intensity (MFI). MFI values were normalized against calibration beads using a linear regression transformation carried out on a log-log scale and reported as equivalent reference fluorophores (ERF). The biomarker evaluable population included all subjects who took at least one dose of study drug and had at least one non-missing pharmacodynamic (PD) assessment. Results were not available for the single subject treated in the 7.5-mg dose group and for one of the two subjects treated in the 15-mg dose group.
Measured: Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose
Part A: Percent Change From Baseline in Levels of Phosphorylated Elongation I Initiation Binding Protein (p4E-BP1) in Stimulated T Cells
Phosphorylated 4E-BP1 is a biomarker for inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Phosphorylated 4E-BP1 was measured in stimulated T cells via flow cytometry. The raw measurements were expressed as median fluorescence intensity (MFI). MFI values were normalized against calibration beads using a linear regression transformation carried out on a log-log scale and reported as equivalent reference fluorophores (ERF). The biomarker evaluable population included all subjects who took at least one dose of study drug and had at least one non-missing pharmacodynamic (PD) assessment. Results were not available for the single subject treated in the 7.5-mg dose group and for one of the two subjects treated in the 15-mg dose group.
Measured: Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose
Part A: Percent Change From Baseline in Levels of Phosphorylated Protein Kinase B (pAKT) in Stimulated Monocytes
Phosphorylated AKT is a biomarker for inhibition of the mammalian target of rapamycin complex 2 (mTORC2). Phosphorylated AKT was measured in stimulated monocytes via flow cytometry. The raw measurements were expressed as median fluorescence intensity (MFI). MFI values were normalized against calibration beads using a linear regression transformation carried out on a log-log scale and reported as equivalent reference fluorophores (ERF). The biomarker evaluable population included all subjects who took at least one dose of study drug and had at least one non-missing pharmacodynamic (PD) assessment. Results were not available for the single subject treated in the 7.5-mg dose group and for one of the two subjects treated in the 15-mg dose group.
Measured: Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in p4E-BP1 in Monocytes by Tumor Cohort
Phosphorylated 4E-BP1 is a biomarker for inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Phosphorylated 4E-BP1 was measured in stimulated monocytes via flow cytometry. MFI values were determined and converted to molecules of equivalent fluorescence label (MEFL) by normalizing against calibration beads. The biomarker evaluable population included all subjects who took at least one dose of study drug and had at least one non-missing pharmacodynamic (PD) assessment. Data is reported by T-cell subsets known as clusters of differentiation (CD).
Measured: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in p4E-BP1 in Monocytes in the HCC and NET Cohorts by Dose
Phosphorylated 4E-BP1 is a biomarker for inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Phosphorylated 4E-BP1 was measured in stimulated monocytes via flow cytometry. MFI values were determined and converted to molecules of equivalent fluorescence label (MEFL) by normalizing against calibration beads. The biomarker evaluable population included all subjects who took at least one dose of study drug and had at least one non-missing pharmacodynamic (PD) assessment. Data is reported by T-cell subsets known as clusters of differentiation (CD).
Measured: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in Levels of pAKT in Monocytes by Tumor Cohort
Phosphorylated AKT is a biomarker for inhibition of the mammalian target of rapamycin complex 2 (mTORC2). Phosphorylated AKT was measured in stimulated monocytes via flow cytometry. MFI values were determined and converted to molecules of equivalent fluorescence label (MEFL) by normalizing against calibration beads. The biomarker evaluable population included all subjects who took at least one dose of study drug and had at least one non-missing pharmacodynamic (PD) assessment.
Measured: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in Levels of pAKT in Monocytes in the HCC and NET Cohorts by Dose
Phosphorylated AKT is a biomarker for inhibition of the mammalian target of rapamycin complex 2 (mTORC2). Phosphorylated AKT was measured in stimulated monocytes via flow cytometry. MFI values were determined and converted to molecules of equivalent fluorescence label (MEFL) by normalizing against calibration beads. The biomarker evaluable population included all subjects who took at least one dose of study drug and had at least one non-missing pharmacodynamic (PD) assessment.
Measured: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in pS6RP Levels in Tumor Tissue by Tumor Type
Tumor tissue biopsies were performed at Baseline and on Day 15 3 hours post dose. Levels of pS6RP were quantified using immunohistochemical (IHC) methods.
Measured: Up to Cycle 1 Day 15 3 hours post dose
Part A: Overall Response Rate
Tumor response was based on Investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors (NSCLC, HCC, NET, and HRPBC), and the International Working Group Criteria (IWC) for DLBCL. Overall Response Rate is defined as the percentage of participants with a best overall response of complete response or partial response. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. In Part A, participants with MM and participants with GBM were not evaluated for tumor response.
Measured: From first dose up to tumor response (approximately 11 months)
Part B: Overall Response Rate
Tumor response was based on Investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors (NSCLC, HCC, NET, and HRPBC), International Working Group Criteria (IWC) for DLBCL, and the International Myeloma Working Group (IMWG) criteria for MM. For GBM, Responses Assessment for Neuro-Oncology Working Group (RANO) criteria were used for tumor response, using the post resection MRI scan as the baseline. Overall Response Rate is defined as the percentage of participants with a best overall response of complete response or partial response. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From first dose up to tumor response (approximately 36 months)
Maximum Observed Concentration (Cmax) of Metabolite M1
Cmax is defined as the maximum observed concentration (in plasma), obtained directly from the observed concentration versus time data. Plasma metabolite M1 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 10.0 ng/mL.
Measured: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Time to Maximum Concentration (Tmax) of Metabolite M1
Tmax is defined as the time to Cmax, obtained directly from the observed concentration versus time data. Plasma metabolite M1 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 10.0 ng/mL.
Measured: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for Metabolite M1
AUCt is defined as the area under the concentration-time curve from Time 0 to the time of the last quantifiable concentration. Plasma metabolite M1 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 10.0 ng/mL.
Measured: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for Metabolite M1
AUC0-24 is defined as the area under the concentration-time curve from Time 0 to 24 hours after a dose. Plasma metabolite M1 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 10.0 ng/mL.
Measured: 0 to 24 hours post-dose on Day -1 and Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Jul 20109 Dec 2016

First posted9 Aug 2010 (estimated)
Study start20 Jul 2010
Primary completion15 Nov 2016
Study completion9 Dec 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Multiple MyelomaStudies of the same condition, open and under way.
More trials run by CelgeneThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 226 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01177397
Sponsor's protocol ID: CC-223-ST-001
Status last verified: Dec 2022
First submitted: 5 Aug 2010
Last updated: 13 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1/2, Multi-Center, Open-Label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTOR Kinase Inhibitor CC-223 Administered Orally to Subjects With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Multiple Myeloma
ClinicalTrials.gov ID: NCT01177397
Acronym / sponsor ID: CC-223-ST-001
Conditions: Multiple Myeloma, Diffuse Large B-Cell Lymphoma, Glioblastoma Multiforme, Hepatocellular Carcinoma, Non-Small Cell Lung Cancer, Neuroendocrine Tumors of Non-Pancreatic Origin
Keywords: Advanced solid malignant neoplasms,Non-Hodgkin Lymphoma,, Multiple Myeloma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 226 participants (actual)
Lead sponsor: CelgeneIndustry (pharma, biotech, devices)
Study start: 20 Jul 2010 (actual)
Primary completion: 15 Nov 2016 (actual)
Study completion: 9 Dec 2016 (actual)
First posted: 9 Aug 2010 (estimated)
Results: Posted 15 Nov 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
CC-223	Experimental	Drug: CC-223All patients will receive CC-223, but serial patient groups will receive different dose levels in Phase 1. The number of groups will be determined by the number of dose levels required to establish dose-limiting toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Histologically-confirmed advanced solid tumor, Non-Hodgkin Lymphoma or multiple myeloma
Patients have not tolerated or progressed on standard therapy, and no further standard therapy is available
Archival and screening tumor biopsy
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (solid tumors), 0-2 (hematologic malignancy)
Adequate organ function

Key exclusion criteria (12 listed)

Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy. Subjects must have recovered from any effects of recent radiotherapy that might confound the safety evaluation of study drug
Symptomatic brain metastases (prior Rx and stable metastases are OK)
Acute or chronic liver or renal disease or pancreatitis
Diarrhea ≥ Grade 2, impaired GI absorption
Impaired cardiac function

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CC-223Part A: (closed to enrollment) Dose level starts with 7.5mg daily taken by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose level is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity). Part B: (closed to enrollment) Optimal dose is administered in 28 day cycles until disease progression.	Drug	CC-223

Primary outcome

Part A: Number of Participants With Dose-limiting Toxicities
Time frame: From first dose up to 30 days after first dose
A dose-limiting toxicity was defined as: - ≥ Grade 3 (per Common Terminology Criteria for Adverse Events [CTCAE] Version 4) clinically relevant adverse event (AE) or laboratory abnormality suspected to be related to CC-223 that commenced within 30 days of first dose, except alopecia, Grade 3 rash of the acneiform or maculopapular type for < 5 days, Grade 3 diarrhea or vomiting lasting < 72 hours, repeated occurrence of Grade 3 hyperuricaemia in subjects with Grade 3 hyperuricemia at baseline, hyperglycemia, hematologic and liver function test (LFT) abnormalities due to disease progression. - Grade 2 fasting hyperglycemia lasting > 14 days or ≥ Grade 3 lasting > 4 days despite optimal medical treatment. - Hematological toxicities including febrile neutropenia, Grade 4 neutropenia or thrombocytopenia for > 7 days, or Grade 3/4 thrombocytopenia with clinically significant bleeding. - Grade 4 LTFs - AE suspected to be CC-223 related necessitating dose reduction during cycle 1.
Maximum Observed Plasma Concentration (Cmax) of CC-223
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Cmax is defined as the maximum observed concentration (in plasma), obtained directly from the observed concentration versus time data. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Time to Maximum Concentration (Tmax) of CC-223
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Tmax is defined as the time to Cmax, obtained directly from the observed concentration versus time data. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for CC-223
Time frame: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for CC-223
Time frame: 0 to 24 hours post-dose on Day -1 and Day 15
AUC0-24 is defined as the area under the concentration-time curve from Time 0 to 24 hours after a dose. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) For CC-223
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
AUCinf is defined as the area under the concentration-time curve from Time 0 extrapolated to infinity. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. AUCinf was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Part A: Terminal Elimination Phase Half-Life (T1/2) of CC-223
Time frame: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. T1/2 was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Apparent Total Body Clearance (CL/F) of CC-223
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
CL/F is defined as the apparent total body clearance when dosed orally, calculated as Dose/AUCinf. Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Apparent Volume of Distribution (Vz/F) of CC-223
Time frame: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose
Plasma CC-223 was measured using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL. VZ/F was not assessed following multiple dosing as the blood sampling schedule on Day 15 did not allow robust assessment of the terminal elimination rate constant.
Part B: Progression Free Survival (PFS) Rate at 6 Months for GBM Participants
Time frame: From first dose to 6 months
Progression free survival rate of GBM participants at 6 months is defined as the percentage of participants without progressive disease per Evaluation Criteria in Solid Tumors (RECIST) 1.1 6 months after starting study treatment. Progressive disease is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

14 secondary outcomes

Part A: Percent Change From Baseline in Levels of Phosphorylated Ribosomal Protein S6 (pS6RP) in Stimulated B Cells
Time frame: Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose
Part A: Percent Change From Baseline in Levels of Phosphorylated Elongation I Initiation Binding Protein (p4E-BP1) in Stimulated T Cells
Time frame: Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose
Part A: Percent Change From Baseline in Levels of Phosphorylated Protein Kinase B (pAKT) in Stimulated Monocytes
Time frame: Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in p4E-BP1 in Monocytes by Tumor Cohort
Time frame: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in p4E-BP1 in Monocytes in the HCC and NET Cohorts by Dose
Time frame: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in Levels of pAKT in Monocytes by Tumor Cohort
Time frame: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in Levels of pAKT in Monocytes in the HCC and NET Cohorts by Dose
Time frame: Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose
Part B: Percent Change From Baseline in pS6RP Levels in Tumor Tissue by Tumor Type
Time frame: Up to Cycle 1 Day 15 3 hours post dose
Part A: Overall Response Rate
Time frame: From first dose up to tumor response (approximately 11 months)
Part B: Overall Response Rate
Time frame: From first dose up to tumor response (approximately 36 months)
Maximum Observed Concentration (Cmax) of Metabolite M1
Time frame: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Time to Maximum Concentration (Tmax) of Metabolite M1
Time frame: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for Metabolite M1
Time frame: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose
Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for Metabolite M1
Time frame: 0 to 24 hours post-dose on Day -1 and Day 15

Results and safety

Results posted to the registry on 15 Nov 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: CC-223 7.5 mg	1	0
Part A: CC-223 15 mg	2	0
Part A: CC-223 30 mg	9	0
Part A: CC-223 45 mg	9	0
Part A: CC-223 60 mg	7	0
Part B: Non-small Cell Lung Cancer (NSCLC)	26	0
Part B: Glioblastoma Multiforme (GBM)	13	0
Part B: Hepatocellular Carcinoma (HCC)	53	0
Part B: Neuroendocrine Tumor (NET)	47	0
Part B: Diffuse Large B-cell Lymphoma (DLBCL)	28	0
Part B: Multiple Myeloma (MM)	14	0
Part B: Hormone Receptor Positive Breast Cancer (HRPBC)	17	0

Primary outcome: Part A: Number of Participants With Dose-limiting Toxicities

Time frame: From first dose up to 30 days after first dose. Count of participants. Unit: Participants

Measure	Part A: CC-223 7.5 mg n = 1	Part A: CC-223 15 mg n = 2	Part A: CC-223 30 mg n = 9	Part A: CC-223 45 mg n = 9	Part A: CC-223 60 mg n = 7
Value	0	0	1	1	2

Population analysed: All treated participants in Part A.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of CC-223

Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Part A: CC-223 7.5 mg n = 1	Part A: CC-223 15 mg n = 2	Part A: CC-223 30 mg n = 8	Part A: CC-223 45 mg n = 9	Part A: CC-223 60 mg n = 7
Day -1	45.8 (NA)	97.4 (57.5)	188 (41.8)	269 (65.7)	319 (70.0)
Day 15	50.8 (NA)	92.0 (162.6)	293 (38.8)	417 (61.6)	480 (88.9)

Population analysed: All treated participants with available pharmacokinetic data in Part A.

Primary outcome: Time to Maximum Concentration (Tmax) of CC-223

Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose. Median (Full Range). Unit: Hours

Measure	Part A: CC-223 7.5 mg n = 1	Part A: CC-223 15 mg n = 2	Part A: CC-223 30 mg n = 8	Part A: CC-223 45 mg n = 9	Part A: CC-223 60 mg n = 7
Day -1/1	1.00 (1.00 to 1.00)	1.25 (1.00 to 1.50)	1.55 (1.00 to 3.20)	3.00 (0.967 to 3.00)	1.50 (1.00 to 5.00)
Day 15	1.50 (1.50 to 1.50)	2.00 (1.00 to 3.00)	1.28 (0.500 to 3.03)	1.63 (0.500 to 8.00)	1.58 (1.00 to 3.00)

Population analysed: All treated participants with available pharmacokinetic data in Part A.

Primary outcome: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for CC-223

Time frame: Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Part A: CC-223 7.5 mg n = 1	Part A: CC-223 15 mg n = 2	Part A: CC-223 30 mg n = 8	Part A: CC-223 45 mg n = 9	Part A: CC-223 60 mg n = 7
Day -1/Day 1	318 (NA)	347 (60.2)	1204 (37.8)	1493 (54.3)	2080 (100.8)
Day 15	179 (NA)	282 (100.7)	1016 (39.2)	1351 (45.0)	1900 (93.5)

Population analysed: All treated participants with available pharmacokinetic data in Part A.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality: From first dose through the course of the trial (up to approximately 6 years). Part A SAEs and AEs: From first dose to 100 days post last dose (up to approximately 14 months). Part B SAEs and AEs: From first dose to 100 days post last dose (up to approximately 49 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: CC-223 7.5 mg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part A: CC-223 15 mg	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Part A: CC-223 30 mg	4 of 9 (44.4%)	8 of 9 (88.9%)	2 of 9
Part A: CC-223 45 mg	4 of 9 (44.4%)	9 of 9 (100%)	3 of 9
Part A: CC-223 60 mg	2 of 7 (28.6%)	7 of 7 (100%)	1 of 7
Part B: Non-small Cell Lung Cancer (NSCLC)	15 of 26 (57.7%)	26 of 26 (100%)	10 of 26
Part B: Glioblastoma Multiforme (GBM)	6 of 13 (46.2%)	13 of 13 (100%)	3 of 13
Part B: Hepatocellular Carcinoma (HCC)	29 of 53 (54.7%)	53 of 53 (100%)	24 of 53
Part B: Neuroendocrine Tumor (NET)	23 of 47 (48.9%)	47 of 47 (100%)	2 of 47
Part B: Diffuse Large B-cell Lymphoma (DLBCL)	17 of 28 (60.7%)	28 of 28 (100%)	5 of 28
Part B: Multiple Myeloma (MM)	6 of 14 (42.9%)	14 of 14 (100%)	2 of 14
Part B: Hormone Receptor Positive Breast Cancer (HRPBC)	11 of 17 (64.7%)	17 of 17 (100%)	4 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bristol-Myers Squibb study director

Bristol-Myers Squibb

16 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CC-223 in people with Multiple Myeloma and Diffuse Large B-Cell Lymphoma, run by Celgene at 16 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, France, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Dose-limiting Toxicities (time frame: From first dose up to 30 days after first dose). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01177397.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2022.