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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT01177397

Collaborator

(none)

173

Enrollment

Locations

Arm

76.7

Actual Duration (Months)

10.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Diffuse Large B-Cell Lymphoma Glioblastoma Multiforme Hepatocellular Carcinoma Non-Small Cell Lung Cancer Neuroendocrine Tumors of Non-Pancreatic Origin Hormone Receptor-Positive Breast Cancer	Drug: CC-223	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

173 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 20, 2010

Actual Primary Completion Date :

Nov 15, 2016

Actual Study Completion Date :

Dec 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CC-223 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.	Drug: CC-223 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.

Arm

Intervention/Treatment

Experimental: CC-223

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.

Drug: CC-223

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.

Outcome Measures

Primary Outcome Measures

Safety [From the time of informed consent, throughout dosing period and for 21 days after the last dose of CC-223]
To determine the safety profile and dose-limiting toxicity of CC-223 using NCI CTCAE v4.
Pharmacokinetics [Throughout the first cycle (30 days) through to the first day of Cycle 2.]
Standard variables (eg. Cmax, AUC, half-life) to define the PK profile for single and multiple doses of oral CC-223.

Secondary Outcome Measures

Pharmacodynamics [Throughout the first cycle (30 days) through to the first day of Cycle 2.]
Phosphorylation inhibition changes by levels of S6, 4EBP (for mTORC1) and AKT (for mTORC2) in circulating granulocytes, and tumor tissue (when available).
Efficacy [Every 2-3 months until proof of tumor progression]
Tumor response rates using appropriate objective criteria for various malignancies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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%
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	UCLA Neuro-Oncology Program	Los Angeles	California	United States	90095
3	University of California, San Francisco Hellen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
4	Moffitt Cancer Center	Tampa	Florida	United States	33612
5	Mayo Clinic Cancer Clinical Studies Unit	Rochester	Minnesota	United States	55905
6	Billings Clinic	Billings	Montana	United States	59102
7	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
8	NYU Cancer Institute - Bellevue Hospital	New York	New York	United States	10016
9	Sarah Cannon Research Institute Drug Development Unit	Nashville	Tennessee	United States	37203
10	Mary Crowley Medical Research Center	Dallas	Texas	United States	75201
11	Institut Claudius Regaud	Toulouse Cedex		France	31052
12	Institut Gustave Roussy Faculte de Medecine Paris Sud Service de pneumologie	Villejuif		France	94800
13	Hospital Universitario de Salamanca	Salamanca		Spain	37007
14	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
15	Sarah Cannon Research Institute UK	London		United Kingdom	W1G 6AD
16	UCL Cancer Institute	London		United Kingdom	WC1E 6BT