4SC-201 (Resminostat) in Advanced Colorectal Carcinoma (SHORE)

4SC

Status and phase

Completed

Phase 2

Phase 1

Conditions

Advanced Colorectal Carcinoma

Treatments

Drug: 4SC-201(Resminostat)

Drug: FOLFIRI

Study type

Interventional

Funder types

Industry

Identifiers

NCT01277406

4SC-201-3-2010

Details and patient eligibility

About

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.

Enrollment

17 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

Exclusion Criteria Phase II arm:

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)).
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