Subjects with advanced solid tumors, non-hodgkin lymphoma (NHL) and multiple myeloma (MM). MedDRA version: 14.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: CC-115
Product Code: CC-115
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CC-115
Current Sponsor code: CC-115
Other descriptive name: CC-115
Concentration unit: mg milligram(s)
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Please refer to protocol section 7.2 for the complete inclusion criteria, which are summarized below. ?Men and women, 18 years or older, with histological or cytological confirmation of advanced unresectable solid tumors, non-hodgkin?s lymphoma (NHL), or multiple myeloma (MM), including those who have progressed on (or not been able to tolerate) standard anticancer therapy or for whom no other conventional therapy exists. Ewing?s sarcoma (ES) subjects may be 12 years or older. ?Consent to screening tumor biopsy (Part A optional; Part B mandatory except as specified for individual tumor types) ?ECOG PS 0 or 1 ?Laboratory values: Absolute neutrophil count (ANC) >= 1.5 x 10^9/L; hemoglobin (Hgb) >= 9 g/dl; platelets >= 100 x 10^9/L; potassium within normal range or correctable with supplements; AST/SGOT and ALT/SGPT = 50 mL/min; negative serum or urine pregnancy test within 72 hrs before starting study treatment in females of childbearing potential Dose expansion part (Part B) of the protocol only: ?Consent to retrieve formalin-fixed, paraffin-embedded (FFPE) archival tumor tissue; an exemption waiver may be granted by the Sponsor in exceptional circumstances. ?Histologically-confirmed tumors of the following types. Please refer to the specific inclusion criteria applicable to each tumor type, described in protocol section 7.2, which are in addition to, or supersede, the above criteria where applicable: -Glioblastoma multiforme (GBM) or gliosarcoma, excluding WHO Grade IV oligoastrocytoma -Head & neck squamous cell cancer (HNSCC) -Triple negative breast cancer (TNBC) -Hormone receptor-positive breast cancer (HRPBC) -Castration-resistant prostate cancer (CRPC) -Ewings Family of Sarcomas Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Please refer to protocol section 7.2 for the complete exclusion criteria, which are summarized below. ?Symptomatic central nervous system metastases ?Known acute or chronic pancreatitis ?Any peripheral neuropathy >= NCI CTCAE grade 2 ?Persistent diarrhea or malabsorption >= NCI CTCAE grade 2, despite medical management. Impaired ability to swallow ?Impaired cardiac function or clinically significant cardiac diseases, including any of the following: LVEF 460 msec on screening ECG (mean of triplicate recordings); unstable angina pectoris or myocardial infarction = 160/95 mmHg) ?Diabetes mellitus on active treatment, or subjects with either fasting blood glucose (FBG) >= 126 mg/dL (7.0 mmol/L), or HbA1c >= 6.5% ?Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol ?Prior systemic cancer-directed treatments or investigational modalities <= 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy ?Major surgery <= 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy ?Pregnancy or breast feeding ?Adults of reproductive potential not employing two forms of birth control (defined in protocol section 7.2): ?Known HIV infection ?Known chronic hepatitis B or C virus (HBV/HCV) infection, unless this is comorbidity in subjects with HCC ?Concurrent active second malignancy for which the subject is receiving therapy, excluding non-melanomatous skin cancer or carcinoma in situ of the cervix Dose expansion part (Part B) of the protocol only: ?Prior treatment with agents targeting both mTOR complexes (dual TORC1+TORC2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated TORC1 inhibitors (e.g., rapalogs) is allowed in both parts of this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: DLT/NTD or MTD are not time-related endpoints;Main Objective: 1. Determine the safety and tolerability of CC-115 when administered orally and to define the Non-Tolerated Dose and the Maximum Tolerated Dose. 2. Determine the PharmacoKinetics of CC-115.;Primary end point(s): 1. The following safety endpoints: DLTs, NTD and MTD, evaluated using the NCI CTCAE criteria Version 4. 2. PK endpoints: Cmax, AUC, tmax, t1/2, CL/F, Vz/F and Accumulation Index of CC-115.;Secondary Objective: 1. Evaluate the extent of inhibition of phosphorylation of S6RP and/or 4E-BP1 for mTORC1 activity and AKT and/or other relevant biomarkers for mTORC2 activity, in blood, skin and/or tumor biopsies/aspirates, when available before and during treatment with CC-115. 2. Evaluate the inhibition of DNA-PK activity in skin samples irradiated by UV light and/or tumor biopsies/aspirates using pDNA-PK S2056 and/or other relevant biomarkers for DNA damage pathways before and during CC-115 treatment. 3. Provide information on the efficacy of CC-115. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Biomarker inhibition, determined by change in the levels of phosphorylation of S6RP, and/or 4E-BP1, and/or AKT, and/or other relevant biomarkers in blood, skin and/or tumor biopsies/aspirates, when available. 2.Inhibition of UV-stimulated DNA-PK activity determined by levels of pDNA-PK and/or other relevant biomarkers in skin and/or tumor biopsies/aspirates, when available. 3.Antitumor efficacy, determined by response rates of each tumor type using tumorappropriate response criteria.;Timepoint(s) of evaluation of this end point: 1. Blood for PD Biomarkers (Part B/US only); 2. UV-stimulated skin biopsy (US only); 3. Antitumor efficacy - Efficacy will be analyzed by each tumor type once all subjects have withdrawn from the study or completed 6 cycles. | — |
Countries
France, Spain, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed