Advanced Colorectal Carcinoma
Conditions
Keywords
Colorectal Carcinoma, Resminostat, HDAC, 4SC-201, Phase I, Phase II
Brief summary
The purpose of this study is to determine the Maximum Tolerated Dose (MTD) of 4SC-201 (Resminostat) in combination with FOLFIRI and whether 4SC-201 (Resminostat) is effective and safe in combination FOLFIRI versus FOLFIRI alone in the treatment of advanced colorectal carcinoma.
Interventions
DRUG4SC-201(Resminostat)
oral administration
DRUGFOLFIRI
i.v. administration
Sponsors
4SC AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase I: * Histologically or cytologically confirmed advanced stage colorectal carcinoma * Documented progression after precedent treatment according to RECIST criteria * 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 * Patients foreseen for chemotherapy with FOLFIRI in second or further line treatment
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 * Therapy with agents known to prolong the QT interval, such as certain antibiotics (e.g. erythromycin, clarithromycin), antidepressants (e.g. doxepin, amitryptiline) or neuroleptics (e.g. haloperidol, clozapine) * 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, availability of UGT1A1 result is not mandatory for study inclusion * Therapy with strong CYP3A4 inhibitors (e.g. ketoconazole) or inductors (e.g. carbamazepine, phenytoin, St. John's Wort) * 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 * Major surgery within the last 4 weeks Inclusion Criteria Phase II : * Histologically or cytologically confirmed advanced stage colorectal carcinoma * Documented progression after precedent treatment according to RECIST criteria * K-ras mutation (which contraindicates EGFR inhibitor therapy, results from local pathology will be accepted for inclusion * 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 * Patients foreseen for chemotherapy with FOLFIRI in second line treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics | — |
| Phase II: Progression free survival (PFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase I: Time to Progression (TTP) | — |
| Phase I: Number of Objective Response (OR) | — |
| Phase I: Overall survival (OS) | — |
| Phase I: Duration of Response (DOR) | — |
| Phase II: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and ever following 8 week (additional 4 cycles each) | — |
| Phase I: Progression free survival (PFS) | — |
| Phase II: Number of Objective Responses (OR) | — |
| Phase II: Duration of Response (DOR) | — |
| Phase II: Safety and tolerability data comprising vital signs, physical examinations, ECGs, clinical laboratory and adverse events | — |
| Phase II: Overall survival (OS) | — |
| Phase II: Pharmacokinetics: AUClast, AUCtau, cmax, tmax, t ½, CL/F of resminostat, Irinotecan (SN-38), 5-FU and folinic acid | — |
| Phase II: Time to Progression (TTP) | — |
| Phase I: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each) | — |
Countries
Germany
Outcome results
None listed