Advanced or metastasized colorectal carcinoma MedDRA version: 15.1 Level: LLT Classification code 10010036 Term: Colorectal carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Resminostat
Product Code: 4SC-201
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Resminostat
CAS Number: 864814-88-0
Current Sponsor code: 4SC-201
Other descriptive name: BKY408
Sponsors
4SC AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase I: - Signed informed consent must be obtained prior to any study specific procedure - Male or female patients, age = 18 years - Histologically or cytologically confirmed advanced stage colorectal carcinoma - Documented progression after precedent treatment according to RECIST criteria - Measurable lesion(s) as defined by modified RECIST criteria (Version 1.1) - ECOG performance status 0 – 2 - Live expectancy of 12 weeks or more - Patients must have previously received treatment with 5-FU alone or in combination with other anti-tumor medications; the required prior treatment with 5-FU can be replaced by the previous use of the respective prodrug capecitabine (Xeloda® ). - Patients foreseen for chemotherapy with FOLFIRI in second or further line treatment - Patients must have adequate bone marrow reserve as evidenced by: Absolute neutrophil count (ANC) = 1,500/µl; Hb = 9 g/dL and platelet count = 75,000/µl - Patients must have a glomerular filtration rate according to MDRD formula of >°60 ml/min/1.73m2 - Patients must have adequate hepatic function as evidenced by a serum bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Phase I: - Patients who have received previous treatment with an HDAC inhibitor - Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study - Patients who have received an investigational therapy within 4 weeks prior to first drug administration in the current study - Any gastrointestinal disorder that could interfere with the absorption of resminostat, such as active ulcerative colitis, Crohn’s disease, diabetic gastroparesis, or other syndromes characterized by malabsorption - Therapy with agents known to prolong the QT interval, such as certain antibiotics (i.e. erythromycin, clarithromycin), antidepressants (i.e. doxepin, amitryptilin) or neuroleptics (i.e. haloperidol, clozapin) - Patients who are homozygous for the UGT1A1 and characterized by the presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter ((TA)7TAA) - Therapy with strong CYP3A4 inhibitors (e.g. ketoconazole) or inductors (e.g. carbamazepine, phenytoin, St. John’s Wort) - Patients who are homozygous for the UGT1A1 and characterized by the presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter ((TA)7TAA). For patients having shown good tolerability of irinotecan in a precedent treatment line according to the investigator´s judgement, the availability of the UGT1A1 result is not mandatory for study inclusion. - Severe internal disease: insufficiently treated or uncontrolled arterial hypertension, hemoptoe, New York Heart Association (NYHA) grade II or greater congestive heart failure, symptomatic coronary heart disease, myocardial infarction (= 12 months prior to inclusion), serious cardiac arrhythmia requiring medication, peripheral arterial occlusive disease stage II or greater, uncontrolled severe disease - Patients with a confirmed QTcF > 480 ms, or a history of additional risk factors for Torsades de Pointes (e.g. heart failure, hypokalemia, family history of long QT syndrome) - Patients with a history of other malignancies unless having undergone definitive treatment more than 5 years prior to entry into the study and without evidence of recurrent malignant disease; Note: patients with basal cell carcinoma of the skin, superficial carcinoma of the bladder, carcinoma of the prostate with a current PSA < 0.1 ng/ml, or cervical intraepithelial neoplasia within the last 5 years are allowed - Patients with any other medical, psychiatric or social condition, which in the opinion of the investigator would preclude participation in the trial, pose an undue medical hazard, interfere with the conduct of the trial or interfere with interpretation of the trial results - Patients with a history of hypersensitivity reactions to compounds of similar chemical or biological composition to resminostat or to any component of the FOLFIRI treatment - Women who are pregnant or lactating or who are planning on becoming pregnant during the trial or for 90 days after completion of the trial - Patients with a history of, who were treated for, or who are suspected of having, hepatitis B, hepatitis C or HIV. Patients suspected of having any of these conditions should undergo appropriate evaluations prior to being enrolled in the study - History or current evidence of clinically relevant allergies or idiosyncrasy to drugs or food - History of organ transplantation - Symptomatic brain and/or CNS metastases - Major surgery within the last 4 weeks - Patients who are employees at the investigational site, re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To determine the MTD of resminostat in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics of resminostat and FOLFIRI Phase II: Progression-free survival (PFS);Secondary Objective: Phase I: - Progression free survival (PFS) - Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each) - Time to Progression (TTP) - Number of Objective Responses (OR) - Overall survival (OS) - Duration of Response (DOR) Phase II: - Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each) - Time to Progression (TTP) - Number of Objective Responses (OR) - Overall survival (OS) - Duration of Response (DOR) - Safety and tolerability - Pharmacokinetics of resminostat and FOLFIRI combination ;Primary end point(s): - Phase I: Potential MTD and optimal dosing schedule of resminostat in combination with FOLFIRI - Phase II: Progression free survival ;Timepoint(s) of evaluation of this end point: At the end of phase I and at the end of phase II | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression free survival (PFS) - Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each) - Time to Progression (TTP) - Number of Objective Responses (OR) - Overall survival (OS) - Duration of Response (DOR) ;Timepoint(s) of evaluation of this end point: At the end of phase I and at the end of phase II | — |
Countries
Germany
Contacts
Public ContactSponsor
4SC AG
Outcome results
None listed