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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01353625
• Other study ID #: CC-115-ST-001
• Status: Completed
• Phase: Phase 1
• Start date: April 25, 2011
• Est. completion date: March 12, 2021

Study information

• Verified date: September 2021
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: March 12, 2021
• Est. primary completion date: March 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Ewing's Osteosarcoma
• Glioblastoma
• Glioblastoma Multiforme
• Hematologic Neoplasms
• Leukemia, Lymphocytic, Chronic, B-Cell
• Neoplasm Metastasis
• Neoplasms
• Osteosarcoma
• Prostate Cancer
• Prostatic Neoplasms
• Squamous Cell Carcinoma of Head and Neck

Intervention

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.

Locations

Country	Name	City	State
France	Gustave Roussy	Villejuif Cedex
Germany	Uniklinik Koln	Koeln
Germany	Universitatsklinikum Wurzburg	Würzburg
Spain	Hospital Val d'Hebron	Barcelona
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Hospital de Donosti	San Sebastián (Guipuzcoa)
Spain	Hospital Virgen del Rocio	Sevilla
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Henry Ford Medical Center - New Center One	Detroit	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	Sarah Cannon Research Institute Drug Development Unit	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute	San Francisco	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain, 

References & Publications (1)

Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodríguez 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Limiting Toxicity		Continuously for 28 days after starting treatment
Primary	Non-Tolerated Dose		Continuously for 28 days after starting treatment
Primary	Maximum Tolerated Dose		Continuously for 28 days after starting treatment
Primary	Maximum Observed Concentration in Plasma of CC-115		Days 1, 2, 15, 16 of treatment
Primary	Area Under the Concentration-Time Curve for CC-115		Days 1, 2, 15 and 16 of treatment
Primary	Time to Maximum Concentration of CC-115		Days 1, 2, 15, and 16 of treatment
Primary	Terminal Half-Life for CC-115		Days 1, 2, 15, and 16 of treatment
Primary	Apparent Total Body Clearance of CC-115		Days 1, 2, 15 and 16 of treatment
Primary	Apparent Volume of Distribution of CC-115		Days 1, 2, 15, and 16 of treatment
Primary	Accumulation Index of CC-115		Days 1, 2, 15 and 16 of treatment
Secondary	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
Secondary	Anti-Tumor Efficacy	Tumor response rates using appropriate objective criteria for various malignancies	Every 2-3 months until proof of tumor progression