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Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.

Primary Purpose

Glioblastoma Multiforme, Squamous Cell Carcinoma of Head and Neck, Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CC-115
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Neoplasm, Malignancy, Carcinoma, Lymphoma, Leukemia, Multiple myeloma, mTOR kinase inhibitor, Castration-resistant prostate cancer, Hormone-resistant prostate cancer, Diffuse Large B-cell lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically-confirmed advanced solid tumor, chronic lymphocytic leukemia, small lymphocytic lymphoma, T-cell prolymphocytic leukemia, Non-Hodgkin Lymphoma or multiple myeloma
  • Progressed or not tolerated standard therapy, and no further standard 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 wks 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
  • 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 mammalian target of rapamycin (mTOR) complexes (dual mammalian target of rapamycin complex 1/2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated target of rapamycin complex 1 (TORC1) inhibitors (eg., rapalogs) is allowed in both parts of this study.

Sites / Locations

  • Cedars-Sinai Medical Center
  • UCLA
  • University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute
  • Moffitt Cancer Center
  • University of Michigan Comprehensive Cancer Center
  • Henry Ford Medical Center - New Center One
  • Memorial Sloan-Kettering Cancer Center
  • Sarah Cannon Research Institute Drug Development Unit
  • Mary Crowley Medical Research Center
  • The University of Texas MD Anderson Cancer Center
  • Gustave Roussy
  • Uniklinik Koln
  • Universitatsklinikum Wurzburg
  • Hospital Val d'Hebron
  • Hospital Universitario Madrid Sanchinarro
  • Hospital de Donosti
  • Hospital Virgen del Rocio

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CC-115

Arm Description

Outcomes

Primary Outcome Measures

Dose-Limiting Toxicity
Non-Tolerated Dose
Maximum Tolerated Dose
Maximum Observed Concentration in Plasma of CC-115
Area Under the Concentration-Time Curve for CC-115
Time to Maximum Concentration of CC-115
Terminal Half-Life for CC-115
Apparent Total Body Clearance of CC-115
Apparent Volume of Distribution of CC-115
Accumulation Index of CC-115

Secondary Outcome Measures

Pharmacodynamics
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).
Anti-Tumor Efficacy
Tumor response rates using appropriate objective criteria for various malignancies

Full Information

First Posted
May 12, 2011
Last Updated
October 4, 2021
Sponsor
Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT01353625
Brief Title
Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.
Official Title
A Phase 1a/1b, Multicenter, Open Label, Dosefinding 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 and Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
April 25, 2011 (Actual)
Primary Completion Date
March 12, 2021 (Actual)
Study Completion Date
March 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 kinase inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor types for later-stage clinical trials. The bioavailability of tablet and capsule formulations under fasting and fed conditions will also be evaluated in some patients.
Detailed Description
Latest amendment clarifies that Chronic Lymophocytic Leukemia (CLL) includes T-cell Prolymphocytic Leukemia (T-PLL). Prior treatment with some drugs targeting mTOR, P13K and related pathways is now permitted.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Squamous Cell Carcinoma of Head and Neck, Prostate Cancer, Ewing's Osteosarcoma, Chronic Lymphocytic Leukemia, Neoplasm Metastasis
Keywords
Neoplasm, Malignancy, Carcinoma, Lymphoma, Leukemia, Multiple myeloma, mTOR kinase inhibitor, Castration-resistant prostate cancer, Hormone-resistant prostate cancer, Diffuse Large B-cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CC-115
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CC-115
Intervention Description
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.
Primary Outcome Measure Information:
Title
Dose-Limiting Toxicity
Time Frame
Continuously for 28 days after starting treatment
Title
Non-Tolerated Dose
Time Frame
Continuously for 28 days after starting treatment
Title
Maximum Tolerated Dose
Time Frame
Continuously for 28 days after starting treatment
Title
Maximum Observed Concentration in Plasma of CC-115
Time Frame
Days 1, 2, 15, 16 of treatment
Title
Area Under the Concentration-Time Curve for CC-115
Time Frame
Days 1, 2, 15 and 16 of treatment
Title
Time to Maximum Concentration of CC-115
Time Frame
Days 1, 2, 15, and 16 of treatment
Title
Terminal Half-Life for CC-115
Time Frame
Days 1, 2, 15, and 16 of treatment
Title
Apparent Total Body Clearance of CC-115
Time Frame
Days 1, 2, 15 and 16 of treatment
Title
Apparent Volume of Distribution of CC-115
Time Frame
Days 1, 2, 15, and 16 of treatment
Title
Accumulation Index of CC-115
Time Frame
Days 1, 2, 15 and 16 of treatment
Secondary Outcome Measure Information:
Title
Pharmacodynamics
Description
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).
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
Title
Anti-Tumor Efficacy
Description
Tumor response rates using appropriate objective criteria for various malignancies
Time Frame
Every 2-3 months until proof of tumor progression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically-confirmed advanced solid tumor, chronic lymphocytic leukemia, small lymphocytic lymphoma, T-cell prolymphocytic leukemia, Non-Hodgkin Lymphoma or multiple myeloma Progressed or not tolerated standard therapy, and no further standard 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 wks 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 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 mammalian target of rapamycin (mTOR) complexes (dual mammalian target of rapamycin complex 1/2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated target of rapamycin complex 1 (TORC1) inhibitors (eg., rapalogs) is allowed in both parts of this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Medical Center - New Center One
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Sarah Cannon Research Institute Drug Development Unit
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Mary Crowley Medical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75201
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77303
Country
United States
Facility Name
Gustave Roussy
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Uniklinik Koln
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universitatsklinikum Wurzburg
City
Würzburg
ZIP/Postal Code
97070
Country
Germany
Facility Name
Hospital Val d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Madrid Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital de Donosti
City
San Sebastián (Guipuzcoa)
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
27235137
Citation
Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodriguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IA, van Kampen RJ, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP. Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood. 2016 Jul 28;128(4):574-83. doi: 10.1182/blood-2016-02-700328. Epub 2016 May 27.
Results Reference
background
PubMed Identifier
31853198
Citation
Munster P, Mita M, Mahipal A, Nemunaitis J, Massard C, Mikkelsen T, Cruz C, Paz-Ares L, Hidalgo M, Rathkopf D, Blumenschein G Jr, Smith DC, Eichhorst B, Cloughesy T, Filvaroff EH, Li S, Raymon H, de Haan H, Hege K, Bendell JC. First-In-Human Phase I Study Of A Dual mTOR Kinase And DNA-PK Inhibitor (CC-115) In Advanced Malignancy. Cancer Manag Res. 2019 Dec 13;11:10463-10476. doi: 10.2147/CMAR.S208720. eCollection 2019.
Results Reference
derived

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Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.

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