4SC-201 (Resminostat) in Advanced Colorectal Carcinoma

Advanced Colorectal Carcinoma Clinical Trial

— SHORE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01277406
• Other study ID #: 4SC-201-3-2010
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 10, 2011
• Last updated: March 31, 2015
• Start date: January 2011
• Est. completion date: February 2015

Study information

• Verified date: March 2015
• Source: 4SC AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: February 2015
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Colorectal Carcinoma
• Carcinoma
• Colorectal Neoplasms

Intervention

Drug:
• 4SC-201(Resminostat)
oral administration
• FOLFIRI
i.v. administration

Locations

Country	Name	City	State
Germany	KTB-Klinik für Tumorbiologie, Klinik für Internistische Onkologie	Freiburg
Germany	University of Heidelberg	Heidelberg
Germany	Universitaetsklinikum Tuebingen; Med. Klinik und Poliklinik II	Tuebingen

Sponsors (1)

Lead Sponsor	Collaborator
4SC AG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics			Yes
Primary	Phase II: Progression free survival (PFS)			No
Secondary	Phase I: Progression free survival (PFS)			No
Secondary	Phase I: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each)			No
Secondary	Phase I: Time to Progression (TTP)			No
Secondary	Phase I: Number of Objective Response (OR)			No
Secondary	Phase I: Overall survival (OS)			No
Secondary	Phase I: Duration of Response (DOR)			No
Secondary	Phase II: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and ever following 8 week (additional 4 cycles each)			No
Secondary	Phase II: Time to Progression (TTP)			No
Secondary	Phase II: Number of Objective Responses (OR)			No
Secondary	Phase II: Duration of Response (DOR)			No
Secondary	Phase II: Safety and tolerability data comprising vital signs, physical examinations, ECGs, clinical laboratory and adverse events			Yes
Secondary	Phase II: Overall survival (OS)			No
Secondary	Phase II: Pharmacokinetics: AUClast, AUCtau, cmax, tmax, t ½, CL/F of resminostat, Irinotecan (SN-38), 5-FU and folinic acid			No