Metastatic, Previously-Treated, Microsatellite-Stable Colorectal Carcinoma MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic
Conditions
Interventions
Product Name: CXD101
Pharmaceutical Form: Capsule
INN or Proposed INN: Not yet assigned
Current Sponsor code: CXD101
Other descriptive n
Sponsors
Celleron Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Written informed consent -Biopsy-confirmed MSS, Mismatch Repair proficient (MMR-P) CRC -Previous first and second line treatment/adjuvant therapy, including use of oxaliplatin and irinotecan unless documented intolerance of these -Measurable disease: longest diameter=10mm (short axis =15mm for nodal lesions) -Age >= 18 years -Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 -Predicted life expectancy > 3 months -Adequate organ and bone marrow function: Hb> 10.0g/dL (may be transfused to this level), neutrophils> 1.5x10^9/L and platelets> 100x10^9/L -Female patients with reproductive potential must have a negative urine and serum pregnancy test prior to starting treatment. -Both women of reproductive potential and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 5 months after discontinuation of treatment -All males with partners of childbearing potential or whose partners are pregnant must use barrier contraception for the duration of dosing and for 5 months post-dosing. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
Exclusion criteria: -Pregnant or breast feeding -Pre-existing auto-immune conditions -Medical conditions requiring systemic immunosuppression -Previous treatment with an HDAC inhibitor or PD1/PDL1 inhibitor -Other chemotherapy, radiotherapy, or investigational therapy within 4 weeks prior to the Screening /Baseline Assessment -Unresolved clinically significant toxicity from a previous treatment -History of recent active chronic inflammatory bowel disease and/or bowel obstruction -Renal function: Serum creatinine >= 1.5 x ULN, or creatinine clearance 3.0; OR total bilirubin >1.5 x ULN. For subjects with involvement of metastatic liver disease: AST > 5.0 x ULN; OR total bilirubin > 3.0 x ULN -Clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure NYHA Class III or IV, or pulmonary disease within 6 months -Symptomatic brain metastasis, uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis -Clinically significant active infection requiring antibiotic or antiretroviral therapy -History of malignancy other than MSS CRC, unless there is the expectation that the malignancy has been cured, and tumour specific treatment for the malignancy has not been administered within the previous 5 years -History of pneumonitis, immune hepatitis or myocarditis, or current uncontrolled thyroid disease -Current positive serology for Hepatitis B or C virus -History of any allergy to excipients of the Investigational Medicinal Products (sodium citrate dihydrate, sodium chloride, mannitol, pentetic acid, Polysorbate 80, sodium hydroxide, hydrochloric acid, hydroxypropyl methylcellulose) -Receipt of any live vaccine 30 days or fewer prior to administration of first dose IMP -Inability to comply with the study protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the Phase Ib element of this study is to define a tolerable combination dose schedule of CXD101 and nivolumab. The primary objective of the Phase II element of this study is to estimate the efficacy MSS CRC tumours of CXD101 in combination with nivolumab by measuring: • Immune Disease Control Rate (iDCR); (ie, complete response [iCR], partial response [iPR], and stable disease [iSD] rate) after Seymour et al, 2017.” ;Timepoint(s) of evaluation of this end point: Every 6 weeks; Secondary Objective: Secondary Objectives are to determine: -Overall survival -immune Objective Response Rate (iCR + iPR) -20-week immune-related progression-free survival -Safety The exploratory objectives of this study are to evaluate tumoural expression of a range of immunological biomarkers (e.g., MHC I & II, PD1, and HR23B expression; T reg cell infiltrates; TAP expression; IL-6) and molecular analyses (mutation/ chromosomal/ epigenetic signatures, and gene expression profiles) that may correlate with effects of study treatment. ; Primary end point(s): Primary endpoint • Phase Ib: the tolerable combination dosing schedule of CXD101 and nivolumab • Phase II: Immune Disease Control Rate (DCR (ie, complete response [iCR], partial response [iPR], and stable disease [SD] rate) after Seymour et al, 2017 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints (Phase Ib and Phase II) • 20-week progression free survival (PFS) • Immune Objective Response Rate (iCR + iPR) • Overall Survival (OS) • Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities ;Timepoint(s) of evaluation of this end point: 20 weeks | — |
Countries
United Kingdom
Contacts
Public ContactClinical Research Director
Celleron Therapeutics Ltd
Outcome results
None listed