Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01277406
Recruitment Status : Completed
First Posted : January 14, 2011
Last Update Posted : April 1, 2015
Sponsor:
Information provided by:
4SC AG

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : January 2011
Actual Primary Completion Date : February 2013
Actual Study Completion Date : February 2015
Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics
  2. Phase II: Progression free survival (PFS)

Secondary Outcome Measures :
  1. Phase I: Progression free survival (PFS)
  2. Phase I: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each)
  3. Phase I: Time to Progression (TTP)
  4. Phase I: Number of Objective Response (OR)
  5. Phase I: Overall survival (OS)
  6. Phase I: Duration of Response (DOR)
  7. Phase II: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and ever following 8 week (additional 4 cycles each)
  8. Phase II: Time to Progression (TTP)
  9. Phase II: Number of Objective Responses (OR)
  10. Phase II: Duration of Response (DOR)
  11. Phase II: Safety and tolerability data comprising vital signs, physical examinations, ECGs, clinical laboratory and adverse events
  12. Phase II: Overall survival (OS)
  13. Phase II: Pharmacokinetics: AUClast, AUCtau, cmax, tmax, t ½, CL/F of resminostat, Irinotecan (SN-38), 5-FU and folinic acid

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01277406


Locations
Layout table for location information
Germany
KTB-Klinik für Tumorbiologie, Klinik für Internistische Onkologie
Freiburg, Germany
University of Heidelberg
Heidelberg, Germany
Universitaetsklinikum Tuebingen; Med. Klinik und Poliklinik II
Tuebingen, Germany
Sponsors and Collaborators
4SC AG
Investigators
Layout table for investigator information
Principal Investigator: Dirk Jäger, Prof. Dr. Medical Oncology National Centre for Tumor Diseases (NCT); University of Heidelberg
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
ClinicalTrials.gov Identifier: NCT01277406    
Other Study ID Numbers: 4SC-201-3-2010
First Posted: January 14, 2011    Key Record Dates
Last Update Posted: April 1, 2015
Last Verified: March 2015
Keywords provided by 4SC AG:
Colorectal Carcinoma
Resminostat
HDAC
 4SC-201
Phase I
Phase II
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
 Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases