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

March 31, 2015 updated by: 4SC AG

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

4SC AG

Investigators

  • Principal Investigator: Dirk Jäger, Prof. Dr., Medical Oncology National Centre for Tumor Diseases (NCT); University of Heidelberg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

January 10, 2011

First Submitted That Met QC Criteria

January 13, 2011

First Posted (Estimate)

January 14, 2011

Study Record Updates

Last Update Posted (Estimate)

April 1, 2015

Last Update Submitted That Met QC Criteria

March 31, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4SC-201-3-2010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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