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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CC-115 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CC-115 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Limiting Toxicity | Continuously for 28 days after starting treatment | |
| Non-Tolerated Dose | Continuously for 28 days after starting treatment | |
| Maximum Tolerated Dose | Continuously for 28 days after starting treatment | |
| Maximum Observed Concentration in Plasma of CC-115 | Days 1, 2, 15, 16 of treatment | |
| Area Under the Concentration-Time Curve for CC-115 | Days 1, 2, 15 and 16 of treatment | |
| Time to Maximum Concentration of CC-115 | Days 1, 2, 15, and 16 of treatment | |
| Terminal Half-Life for CC-115 | Days 1, 2, 15, and 16 of treatment | |
| Apparent Total Body Clearance of CC-115 | Days 1, 2, 15 and 16 of treatment | |
| Apparent Volume of Distribution of CC-115 | Days 1, 2, 15, and 16 of treatment | |
| Accumulation Index of CC-115 | Days 1, 2, 15 and 16 of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States | ||
| UCLA |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27235137 | Background | 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. | |
| 31853198 |
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|
| Anti-Tumor Efficacy | Tumor response rates using appropriate objective criteria for various malignancies | Every 2-3 months until proof of tumor progression |
| Los Angeles |
| California |
| 90095 |
| United States |
| University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute | San Francisco | California | 94115 | United States |
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Henry Ford Medical Center - New Center One | Detroit | Michigan | 48202 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10021 | United States |
| Sarah Cannon Research Institute Drug Development Unit | Nashville | Tennessee | 37203 | United States |
| Mary Crowley Medical Research Center | Dallas | Texas | 75201 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77303 | United States |
| Gustave Roussy | Villejuif | 94805 | France |
| Uniklinik Koln | Cologne | 50937 | Germany |
| Universitatsklinikum Wurzburg | Würzburg | 97070 | Germany |
| Hospital Val d'Hebron | Barcelona | 08035 | Spain |
| Hospital Universitario Madrid Sanchinarro | Madrid | 28050 | Spain |
| Hospital de Donosti | San Sebastián (Guipuzcoa) | 20014 | Spain |
| Hospital Virgen del Rocio | Seville | 41013 | Spain |
| Derived |
| 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. |
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D011471 | Prostatic Neoplasms |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D009362 | Neoplasm Metastasis |
| D009369 | Neoplasms |
| D002277 | Carcinoma |
| D008223 | Lymphoma |
| D007938 | Leukemia |
| D009101 | Multiple Myeloma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D002294 | Carcinoma, Squamous Cell |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009385 | Neoplastic Processes |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
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| ID | Term |
|---|---|
| C000601954 | 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one |
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