Advanced Colorectal CarcinomaPhase 1/2SHORENCT01277406
4SC-201 (Resminostat) in Advanced Colorectal Carcinoma
A Phase 1/2 study testing 4SC-201(Resminostat) and FOLFIRI in people with Advanced Colorectal Carcinoma, run by 4SC AG at 3 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Colorectal Carcinoma
- What is being tested?
- 4SC-201(Resminostat) and FOLFIRI
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesGermany
- Study dates
- Jan 2011to Feb 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
KTB-Klinik für Tumorbiologie, Klinik für Internistische Onkologie
Freiburg im Breisgau
University of Heidelberg
Heidelberg
Universitaetsklinikum Tuebingen; Med. Klinik und Poliklinik II
Tübingen
About this study
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
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.
- Conditions
- Advanced Colorectal Carcinoma
- Being tested
- 4SC-201(Resminostat), FOLFIRI
- Keywords
- Colorectal Carcinoma, Resminostat, HDAC, 4SC-201, Phase I, Phase II
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4SC-201(Resminostat)Drug
oral administration
FOLFIRIDrug
i.v. administration
| Study group | Role | What they receive |
|---|---|---|
| 4SC-201+FOLFIRI | Experimental | Not described Receives: Drug: 4SC-201(Resminostat); Drug: FOLFIRI |
| FOLFIRI | Active comparator | Not described Receives: Drug: FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics
Phase II: Progression free survival (PFS)
Secondary outcomes (13)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionFeb 2013
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Colorectal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- 4SC AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Dirk Jäger, Prof. Dr., Principal investigator, Medical Oncology National Centre for Tumor Diseases (NCT); University of Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01277406
- Sponsor's protocol ID
- 4SC-201-3-2010
- Acronym
- SHORE
- Status last verified
- Mar 2015
- First submitted
- 10 Jan 2011
- Last updated
- 1 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01277406
- Acronym / sponsor ID
- SHORE / 4SC-201-3-2010
- Conditions
- Advanced Colorectal Carcinoma
- Keywords
- Colorectal Carcinoma, Resminostat, HDAC, 4SC-201, Phase I, Phase II
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- 4SC AGIndustry (pharma, biotech, devices)
- Study start
- Jan 2011
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 14 Jan 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 4SC-201+FOLFIRI | Experimental | Drug: 4SC-201(Resminostat), Drug: FOLFIRI |
| FOLFIRI | Active comparator | Drug: FOLFIRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4SC-201(Resminostat)oral administration | Drug | 4SC-201+FOLFIRI |
| FOLFIRIi.v. administration | Drug | 4SC-201+FOLFIRI, FOLFIRI |
Primary outcome
Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics
Phase II: Progression free survival (PFS)
13 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dirk Jäger, Prof. Dr. principal investigator
Medical Oncology National Centre for Tumor Diseases (NCT); University of Heidelberg
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 4SC-201(Resminostat) and FOLFIRI in people with Advanced Colorectal Carcinoma, run by 4SC AG at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: MTD of 4SC-201 (Resminostat) in combination with FOLFIRI by investigating safety, tolerability and pharmacokinetics. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2015.