A phase I/II study to evaluate safety, tolerability, pharmacokinetics and efficacy of resminostat (4SC-201) in combination with a second-line treatment in patients with k-ras mutated advanced colorectal carcinoma - SHORE-study

4SC AG0 sites80 target enrollmentJune 28, 2010

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Not specified
Sponsor: 4SC AG
Enrollment: 80
Status: Active, not recruiting
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

June 28, 2010

End Date

TBD

Last Updated

10 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

4SC AG

Eligibility Criteria

Inclusion Criteria

•\- 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

Exclusion Criteria

•\- 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)