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

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ClinicalTrials.gov Identifier: NCT01277406
Recruitment Status : Completed
First Posted : January 14, 2011
Last Update Posted : April 1, 2015
Sponsor:
Information provided by:
4SC AG

Tracking Information
First Submitted Date  ICMJE January 10, 2011
First Posted Date  ICMJE January 14, 2011
Last Update Posted Date April 1, 2015
Study Start Date  ICMJE January 2011
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2011)
  • Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics
  • Phase II: Progression free survival (PFS)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2011)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 4SC-201 (Resminostat) in Advanced Colorectal Carcinoma
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Colorectal Carcinoma
Intervention  ICMJE
  • Drug: 4SC-201(Resminostat)
    oral administration
  • Drug: FOLFIRI
    i.v. administration
Study Arms  ICMJE
  • Experimental: 4SC-201+FOLFIRI
    Interventions:
    • Drug: 4SC-201(Resminostat)
    • Drug: FOLFIRI
  • Active Comparator: FOLFIRI
    Intervention: Drug: FOLFIRI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 15, 2014)
17
Original Estimated Enrollment  ICMJE
 (submitted: January 13, 2011)
80
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01277406
Other Study ID Numbers  ICMJE 4SC-201-3-2010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE 4SC AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dirk Jäger, Prof. Dr. Medical Oncology National Centre for Tumor Diseases (NCT); University of Heidelberg
PRS Account 4SC AG
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP