4SC-201 (Resminostat) in Advanced Colorectal Carcinoma (SHORE)
Primary Purpose
Advanced Colorectal Carcinoma
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
4SC-201(Resminostat)
FOLFIRI
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Colorectal Carcinoma focused on measuring Colorectal Carcinoma, Resminostat, HDAC, 4SC-201, Phase I, Phase II
Eligibility 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
Sites / Locations
- KTB-Klinik für Tumorbiologie, Klinik für Internistische Onkologie
- University of Heidelberg
- Universitaetsklinikum Tuebingen; Med. Klinik und Poliklinik II
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
4SC-201+FOLFIRI
FOLFIRI
Arm Description
Outcomes
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01277406
Brief Title
4SC-201 (Resminostat) in Advanced Colorectal Carcinoma
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2015 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
4SC AG
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Colorectal Carcinoma
Keywords
Colorectal Carcinoma, Resminostat, HDAC, 4SC-201, Phase I, Phase II
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
4SC-201+FOLFIRI
Arm Type
Experimental
Arm Title
FOLFIRI
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
4SC-201(Resminostat)
Intervention Description
oral administration
Intervention Type
Drug
Intervention Name(s)
FOLFIRI
Intervention Description
i.v. administration
Primary Outcome Measure Information:
Title
Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics
Title
Phase II: Progression free survival (PFS)
Secondary Outcome Measure Information:
Title
Phase I: Progression free survival (PFS)
Title
Phase I: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each)
Title
Phase I: Time to Progression (TTP)
Title
Phase I: Number of Objective Response (OR)
Title
Phase I: Overall survival (OS)
Title
Phase I: Duration of Response (DOR)
Title
Phase II: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and ever following 8 week (additional 4 cycles each)
Title
Phase II: Time to Progression (TTP)
Title
Phase II: Number of Objective Responses (OR)
Title
Phase II: Duration of Response (DOR)
Title
Phase II: Safety and tolerability data comprising vital signs, physical examinations, ECGs, clinical laboratory and adverse events
Title
Phase II: Overall survival (OS)
Title
Phase II: Pharmacokinetics: AUClast, AUCtau, cmax, tmax, t ½, CL/F of resminostat, Irinotecan (SN-38), 5-FU and folinic acid
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk Jäger, Prof. Dr.
Organizational Affiliation
Medical Oncology National Centre for Tumor Diseases (NCT); University of Heidelberg
Official's Role
Principal Investigator
Facility Information:
Facility Name
KTB-Klinik für Tumorbiologie, Klinik für Internistische Onkologie
City
Freiburg
Country
Germany
Facility Name
University of Heidelberg
City
Heidelberg
Country
Germany
Facility Name
Universitaetsklinikum Tuebingen; Med. Klinik und Poliklinik II
City
Tuebingen
Country
Germany
12. IPD Sharing Statement
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4SC-201 (Resminostat) in Advanced Colorectal Carcinoma
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