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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
4SC AG
ClinicalTrials.gov Identifier:
NCT01277406
First received: January 10, 2011
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Advanced Colorectal Carcinoma
Drug: 4SC-201(Resminostat)
Drug: FOLFIRI
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Further study details as provided by 4SC AG:

Primary Outcome Measures:
  • Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics [ Designated as safety issue: Yes ]
  • Phase II: Progression free survival (PFS) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase I: Progression free survival (PFS) [ Designated as safety issue: No ]
  • Phase I: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and every following 8 weeks (additional 4 cycles each) [ Designated as safety issue: No ]
  • Phase I: Time to Progression (TTP) [ Designated as safety issue: No ]
  • Phase I: Number of Objective Response (OR) [ Designated as safety issue: No ]
  • Phase I: Overall survival (OS) [ Designated as safety issue: No ]
  • Phase I: Duration of Response (DOR) [ Designated as safety issue: No ]
  • Phase II: Progression free survival rate (PFSR) after 8 weeks (4 cycles) and ever following 8 week (additional 4 cycles each) [ Designated as safety issue: No ]
  • Phase II: Time to Progression (TTP) [ Designated as safety issue: No ]
  • Phase II: Number of Objective Responses (OR) [ Designated as safety issue: No ]
  • Phase II: Duration of Response (DOR) [ Designated as safety issue: No ]
  • Phase II: Safety and tolerability data comprising vital signs, physical examinations, ECGs, clinical laboratory and adverse events [ Designated as safety issue: Yes ]
  • Phase II: Overall survival (OS) [ Designated as safety issue: No ]
  • Phase II: Pharmacokinetics: AUClast, AUCtau, cmax, tmax, t ½, CL/F of resminostat, Irinotecan (SN-38), 5-FU and folinic acid [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: January 2011
Estimated Study Completion Date: June 2014
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 4SC-201+FOLFIRI Drug: 4SC-201(Resminostat)
oral administration
Drug: FOLFIRI
i.v. administration
Active Comparator: FOLFIRI Drug: FOLFIRI
i.v. administration

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01277406

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

No publications provided

ClinicalTrials.gov Identifier: NCT01277406     History of Changes
Other Study ID Numbers: 4SC-201-3-2010
Study First Received: January 10, 2011
Last Updated: January 15, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by 4SC AG:
Colorectal Carcinoma
Resminostat
HDAC
4SC-201
Phase I
Phase II

Additional relevant 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

ClinicalTrials.gov processed this record on September 30, 2014