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

Sponsor

4SC AG (Industry)

Overall Status

Completed

CT.gov ID

NCT01277406

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

5.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Colorectal Carcinoma	Drug: 4SC-201(Resminostat) Drug: FOLFIRI	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4SC-201+FOLFIRI	Drug: 4SC-201(Resminostat) oral administration Drug: FOLFIRI i.v. administration
Active Comparator: FOLFIRI	Drug: FOLFIRI i.v. administration

Arm

Intervention/Treatment

Experimental: 4SC-201+FOLFIRI

Drug: 4SC-201(Resminostat)

oral administration

Drug: FOLFIRI

i.v. administration

Active Comparator: FOLFIRI

Drug: FOLFIRI

i.v. administration

Outcome Measures

Primary Outcome Measures

Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics []
Phase II: Progression free survival (PFS) []

Secondary Outcome Measures

Phase I: Progression free survival (PFS) []
Phase I: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each) []
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 II: Time to Progression (TTP) []
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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	KTB-Klinik für Tumorbiologie, Klinik für Internistische Onkologie	Freiburg	Germany
2	University of Heidelberg	Heidelberg	Germany
3	Universitaetsklinikum Tuebingen; Med. Klinik und Poliklinik II	Tuebingen	Germany