Clinical trial NCT01353625: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2011-05-13
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Dose-Limiting Toxicity
timeFrame: Continuously for 28 days after starting treatment
measure: Non-Tolerated Dose
timeFrame: Continuously for 28 days after starting treatment
measure: Maximum Tolerated Dose
timeFrame: Continuously for 28 days after starting treatment
measure: Maximum Observed Concentration in Plasma of CC-115
timeFrame: Days 1, 2, 15, 16 of treatment
measure: Area Under the Concentration-Time Curve for CC-115
timeFrame: Days 1, 2, 15 and 16 of treatment
measure: Time to Maximum Concentration of CC-115
timeFrame: Days 1, 2, 15, and 16 of treatment
measure: Terminal Half-Life for CC-115
timeFrame: Days 1, 2, 15, and 16 of treatment
measure: Apparent Total Body Clearance of CC-115
timeFrame: Days 1, 2, 15 and 16 of treatment
measure: Apparent Volume of Distribution of CC-115
timeFrame: Days 1, 2, 15, and 16 of treatment
measure: Accumulation Index of CC-115
timeFrame: Days 1, 2, 15 and 16 of treatment
Secondary outcomes:
measure: Pharmacodynamics
timeFrame: Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment
measure: Anti-Tumor Efficacy
timeFrame: Every 2-3 months until proof of tumor progression
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Medical Center - New Center One
state: Michigan
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Drug Development Unit
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Koeln
country: Germany
facility: Uniklinik Koln
city: Würzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Barcelona
country: Spain
facility: Hospital Val d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: San Sebastián (Guipuzcoa)
country: Spain
facility: Hospital de Donosti
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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.
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.