Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, Non-Hodgkin's Lymphoma or Multiple Myeloma

This study is currently recruiting participants.

Verified October 2012 by Celgene Corporation

Sponsor:

Information provided by (Responsible Party):

Celgene Corporation

ClinicalTrials.gov Identifier:

NCT01353625

First received: May 12, 2011

Last updated: October 19, 2012

Last verified: October 2012

History of Changes

Tracking Information

First Received Date ^ICMJE

May 12, 2011

Last Updated Date

October 19, 2012

Start Date ^ICMJE

April 2011

Estimated Primary Completion Date

December 2014 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Dose-Limiting Toxicity [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
Non-Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
Maximum Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
Maximum Observed Concentration in Plasma of CC-115 [ Time Frame: Days 1, 2, 15, 16 of treatment ] [ Designated as safety issue: Yes ]
Area Under the Concentration-Time Curve for CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
Time to Maximum Concentration of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
Terminal Half-Life for CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
Apparent Total Body Clearance of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
Apparent Volume of Distribution of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
Accumulation Index of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]

Original Primary Outcome Measures ^ICMJE

Dose-Limiting Toxicity [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
Dose-Limiting Toxicity
Non-Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
Maximum Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
Maximum Observed Concentration in Plasma of CC-115 [ Time Frame: Days 1, 2, 15, 16 of treatment ] [ Designated as safety issue: Yes ]
Area Under the Concentration-Time Curve for CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
Time to Maximum Concentration of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
Terminal Half-Life for CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
Apparent Total Body Clearance of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
Apparent Volume of Distribution of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
Accumulation Index of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]

Change History

Complete list of historical versions of study NCT01353625 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Pharmacodynamics [ Time Frame: Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment ] [ Designated as safety issue: No ]
Phosphorylation inhibition determined by changes in the levels of multiple biomarkers including S6 and, 4EBP (for mTORC1), AKT (for mTORC2) and other appropriate biomarkers in circulating granulocytes and tumor tissue (when available).
Inhibition of biomarker DNA-PK activity in skin biopsies. [ Time Frame: Screening (within 28 days prior to first dose of study drug) and Day 15 ] [ Designated as safety issue: No ]
Number of participants with tumor response using appropriate objective criteria. [ Time Frame: Screening (within 28 days prior to first dose of study drug), periodically during treatment, (every 2-3 months while on study drug), and end of treatment ] [ Designated as safety issue: No ]

Original Secondary Outcome Measures ^ICMJE

Pharmacodynamics [ Time Frame: Screening and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment ] [ Designated as safety issue: No ]
Phosphorylation inhibition determined by changes in the levels of multiple biomarkers including S6 and, 4EBP (for mTORC1), AKT (for mTORC2) and other appropriate biomarkers in circulating granulocytes and tumor tissue (when available).
Inhibition of biomarker DNA-PK activity in skin biopsies. [ Time Frame: Screening and Day 15 ] [ Designated as safety issue: No ]
Number of participants with tumor response using appropriate objective criteria. [ Time Frame: Screening, Days 15 and 155 and end of treatment ] [ Designated as safety issue: No ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, Non-Hodgkin's Lymphoma or Multiple Myeloma

Official Title ^ICMJE

A Phase 1a/1b, Multicenter, Open Label, Dose-Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Dual DNA-PK and TOR Kinase Inhibitor, CC-115, Administered Orally to Subjects With Advanced Solid Tumors, Non-Hodgkin's Lymphoma or Multiple Myeloma

Brief Summary

The main purpose of this first human study with CC-115 is to assess the safety and action of a new class of experimental drug (dual DNA-PK and TOR inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dosing level and regimen for later-stage clinical trials.

Detailed Description

Minimum age limit is 18 years however subjects with Ewings sarcoma may be 12 years or older

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Multiple Myeloma
Non-Hodgkin's Lymphoma
Glioblastoma Multiforme
Head and Neck Squamous Cell Cancer
Triple Negative Breast Cancer
Castration-Resistant Prostate Cancer
Hormone Receptor-Positive Breast Cancer
Ewing's Family of Sarcomas

Intervention ^ICMJE

Drug: CC-115

Part A (actively recruiting): Dose level starts with 0.5mg daily by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose schedule is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity).

Part B: Optimal dose schedule is administered in 28-day cycles until disease progression.

Study Arm (s)

Experimental: CC-115

Intervention: Drug: CC-115

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

160

Estimated Completion Date

March 2015

Estimated Primary Completion Date

December 2014 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Histologically-confirmed advanced solid tumor, Non-Hodgkin's Lymphoma or multiple myeloma (Phase 1a); Glioblastoma multiforme, head & neck squamous cell cancer, triple negative breast cancer, hormone receptor-positive breast cancer, castration-resistant prostate cancer, Ewing's family of sarcoma (Phase 1b)
Progressed or not tolerated standard therapy, and no further conventional therapy is available
Archival and screening tumor biopsy
Eastern Cooperative Oncology Group Performance Status 0 or 1
Adequate organ function

Exclusion Criteria:

Prior cancer-directed modalities or investigational drugs within 4 weeks or 5 half lives, whichever is shorter
Symptomatic brain metastases (prior treatment and stable metastases are allowed)
Acute or chronic renal disease or pancreatitis
Diarrhea ≥ Grade 2, impaired gastrointestinal absorption
Impaired cardiac function
History of diabetes requiring treatment, glucose >126 mg/dL, Glycated hemoglobin (HbA1c) ≥6.5%
Peripheral neuropathy ≥ Grade 2
Pulmonary fibrosis
Known Human Immunodeficiency Virus (HIV) infection, chronic hepatitis B or C (unless associated with hepatocellular cancer)
Pregnant, inadequate contraception, breast feeding
Most concurrent second malignancies
Part B only: Prior treatment with agents targeting both mTOR complexes (dual TORC1+TORC2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated TORC1 inhibitors (eg., rapalogs) is allowed in both parts of this study.

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Wayne R. Hull

1-908-673-9727

whull@celgene.com

Location Countries ^ICMJE

United States, France, Spain

Administrative Information

NCT Number ^ICMJE

NCT01353625

Other Study ID Numbers ^ICMJE

CC-115-ST-001

Has Data Monitoring Committee

Responsible Party

Celgene Corporation

Study Sponsor ^ICMJE

Celgene Corporation

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Kristen Hege, MD

Celgene Corporation

Information Provided By

Celgene Corporation

Verification Date

October 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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