Colorectal NeoplasmsPhase 2NCT01289821
First Line Treatment of Metastatic Colorectal Cancer With mFOLFOX6 in Combination With Regorafenib
A Phase 2 study testing Regorafenib (Stivarga, BAY73-4506), Oxaliplatin and Folinic acid in people with Colorectal Neoplasms, run by Bayer at 18 sites in 7 countries.
Trial summary
This is a study to evaluate the efficacy (effectiveness) and the safety of regorafenib when given in combination with chemotherapy mFOLFOX6 as first line therapy in patients with metastatic colorectal cancer (CRC). mFOLFOX6 is an approved chemotherapy. Regorafenib is an oral (i.e. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Regorafenib (Stivarga, BAY73-4506), Oxaliplatin and Folinic acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 18 sitesin 7 countries
- Study dates
- Feb 2011to Jun 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male or female subjects aged ≥ 18 years
- Histological or cytological documentation of adenocarcinoma of the colon or rectum
- Suitable to receive mFOLFOX6 regimen as first line metastatic treatment
- At least 1 measurable lesion as per RECIST version 1.1
- Unresectable or unlikely becoming resectable metastatic disease
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy of at least 3 months
- Adequate bone marrow, liver, and renal function
Who cannot join
- Prior systemic anticancer therapy for metastatic colorectal cancer (CRC). Adjuvant chemotherapy for CRC (Stage I, II, III) is permitted, if the adjuvant therapy ended > 6 months before screening and recurrent disease was documented.
- Prior treatment with antivascular endothelial growth factor (anti-VEGF) agents and any signal transduction inhibitors (STIs)
- Uncontrolled hypertension
- Subjects with symptoms, signs, or history of brain metastases
- Any hemorrhage or bleeding event ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 4 weeks of start of study treatment
- Sensory neuropathy (> CTCAE Grade 1), unresolved toxicity > CTCAE Grade 1 attributed to any prior therapy/procedure excluding alopecia
Trial locations and contacts
18 sites in 7 countries.
18 sites in 7 countries
Germany4 sites
Study site
Dresden, Saxony, 01307
Study site
Herne, North Rhine-Westphalia, 44625
Study site
Oldenburg, Lower Saxony, 26133
Study site
Stuttgart, Baden-Wurttemberg, 70199
Belgium3 sites
Study site
Bruxelles - Brussel, 1070
Study site
Edegem, 2650
Study site
Leuven, 3000
Italy3 sites
Study site
Ancona, The Marches, 60126
Study site
Genoa, Liguria, 16132
Study site
Naples, Campania, 80131
Spain3 sites
Study site
Barcelona, Barcelona, 08035
Study site
Madrid, Madrid, 28034
Study site
Santander, Cantabria, 39008
Australia2 sites
Study site
Concord, New South Wales, 2139
Study site
Woodville South, South Australia, 5011
United Kingdom2 sites
Study site
Glasgow, G12 0YN
Study site
Manchester, Manchester, M20 4BX
About this study
Official title: An Uncontrolled, Open-label, Phase II Study in Subjects With Metastatic Adenocarcinoma of the Colon or Rectum Who Are Receiving First Line Chemotherapy With mFOLFOX6 (Oxaliplatin/ Folinic Acid/5-fluorouracil [5-FU]) in Combination With Regorafenib
This is a study to evaluate the efficacy (effectiveness) and the safety of regorafenib when given in combination with chemotherapy mFOLFOX6 as first line therapy in patients with metastatic colorectal cancer (CRC). mFOLFOX6 is an approved chemotherapy. Regorafenib is an oral (i.e. taken by mouth) multi-targeted kinase inhibitor. A kinase inhibitor targets certain key proteins that are essential for the survival of the cancer cell. By specifically targeting these proteins, regorafenib may stop cancer growth. The growth of the tumor may be decreased by preventing these specific proteins from functioning.
The primary endpoint (the most meaningful result to be tracked) of this study is based on the rate of response, i.e. the disease getting smaller. The aim is to show that the therapy of colorectal cancer with mFOLFOX6 in combination with regorafenib improves the response rate observed for the standard therapy only.
- Conditions
- Colorectal Neoplasms
- Being tested
- Regorafenib (Stivarga, BAY73-4506), Oxaliplatin, Folinic acid, 5-FU (mFOLFOX6)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib (Stivarga, BAY73-4506)Drug
Subjects will receive regorafenib 160 mg od on days 4 to 10 and days 18 to 24 as four 40 mg coprecipitate tablets. In case of administration as a single agent during the study, regorafenib will be administered 160 mg od for 3 weeks on/1 week off. Each cycle consists of 28 days.
OxaliplatinDrug
On day 1 and day 15 of each cycle, participants will receive 85 mg/m^2 oxaliplatin as a 2 hour i.v. infusion.
Folinic acidDrug
On day 1 and day 15 of each cycle, participants will receive folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2 hour i.v. infusion.
5-FU (mFOLFOX6)Drug
Participants will receive a 400 mg/m^2 5 FU i.v. bolus injection immediately followed by a 2400 mg/m^2 5 FU 46 hour i.v. infusion.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) | Experimental | On Day 1, participants received 85 mg/m^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. Receives: Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Oxaliplatin; Drug: Folinic acid; Drug: 5-FU (mFOLFOX6) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response (OR)
OR was defined as the best tumor response (confirmed complete response [CR] or partial response [PR]) observed by MRI or CT scan assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). Any pathological lymph nodes (whether target or non target) must have a reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing nontarget lesions and no appearance of new lesions.
Measured: From start of treatment until 30 days after termination of study medication, an average of 47 weeks. Assessed every 8 weeks.
Secondary outcomes (5)
Overall Survival (OS)
OS was calculated as the time from first date of receiving study treatment to date of death due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.
Measured: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Progression-free Survival (PFS)
PFS was defined as time from the date of start of study treatment to the date of first observed disease progression (radiological according to central assessment or clinical), or death due to any cause, if death occurred before progression was documented. PFS for participants without disease progression or death at the date of database cutoff were right-censored at the last date of tumor assessment. Participants who had no tumor evaluation after baseline and no clinical progression post baseline and who did not die were censored at Day 1 in the analysis. PD = At least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non target lesions or the appearance of one or more new lesions will also constitute PD.
Measured: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Disease Control (DC)
DC was defined as the proportion of participants who had a best response rating of CR, PR, or stable disease (SD) according to RECIST criteria that was achieved during treatment or within 30 days after termination of study treatment. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. A minimum of 8 weeks (allowing a minus 7-day time window) between start of study treatment and the first follow-up tumor assessment with SD as response was required to assign SD as best overall response.
Measured: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Duration of Response (DOR)
DOR was defined as the time from the date of first documented objective response of PR or CR, whichever was noted earlier, to first subsequent disease progression or death (if death occurred before progression was documented). DOR was defined for responders only (that is, subjects with CR or PR). DOR for subjects without disease progression or death before progression was right censored at the date of their last tumor assessment.
Measured: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Duration of Stable Disease (DOSD)
DOSD was only evaluated in participants failing to achieve a best response of CR or PR, but who achieved SD. DOSR was defined as the time (in days) from date of start of study treatment to the date at which disease progression or death (if death occurred before progression was first documented). The date the tumor scan was performed was used for this calculation. DOSD for participants without disease progression or death before progression at the time of analysis were censored at the date of their last tumor assessment.
Measured: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionMar 2012
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01289821
- Sponsor's protocol ID
- 11728
- Other IDs
- 2010-020121-41
- Status last verified
- Mar 2017
- First submitted
- 3 Feb 2011
- Last updated
- 15 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Schultheis B, Folprecht G, Kuhlmann J, Ehrenberg R, Hacker UT, Kohne CH, Kornacker M, Boix O, Lettieri J, Krauss J, Fischer R, Hamann S, Strumberg D, Mross KB. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol. 2013 Jun;24(6):1560-7. doi: 10.1093/annonc/mdt056. Epub 2013 Mar 13.
PubMed 23493136
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Uncontrolled, Open-label, Phase II Study in Subjects With Metastatic Adenocarcinoma of the Colon or Rectum Who Are Receiving First Line Chemotherapy With mFOLFOX6 (Oxaliplatin/ Folinic Acid/5-fluorouracil [5-FU]) in Combination With Regorafenib
- ClinicalTrials.gov ID
- NCT01289821
- Acronym / sponsor ID
- 11728
- Conditions
- Colorectal Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 4 Feb 2011 (estimated)
- Results
- Posted 4 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to evaluate the efficacy (effectiveness) and the safety of regorafenib when given in combination with chemotherapy mFOLFOX6 as first line therapy in patients with metastatic colorectal cancer (CRC). mFOLFOX6 is an approved chemotherapy. Regorafenib is an oral (i.e. taken by mouth) multi-targeted kinase inhibitor. A kinase inhibitor targets certain key proteins that are essential for the survival of the cancer cell. By specifically targeting these proteins, regorafenib may stop cancer growth. The growth of the tumor may be decreased by preventing these specific proteins from functioning.
The primary endpoint (the most meaningful result to be tracked) of this study is based on the rate of response, i.e. the disease getting smaller. The aim is to show that the therapy of colorectal cancer with mFOLFOX6 in combination with regorafenib improves the response rate observed for the standard therapy only.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) | Experimental | Drug: Regorafenib (Stivarga, BAY73-4506), Drug: Oxaliplatin, Drug: Folinic acid, Drug: 5-FU (mFOLFOX6)On Day 1, participants received 85 mg/m^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female subjects aged ≥ 18 years
- Histological or cytological documentation of adenocarcinoma of the colon or rectum
- Suitable to receive mFOLFOX6 regimen as first line metastatic treatment
- At least 1 measurable lesion as per RECIST version 1.1
- Unresectable or unlikely becoming resectable metastatic disease
Key exclusion criteria (6 listed)
- Prior systemic anticancer therapy for metastatic colorectal cancer (CRC). Adjuvant chemotherapy for CRC (Stage I, II, III) is permitted, if the adjuvant therapy ended > 6 months before screening and recurrent disease was documented.
- Prior treatment with antivascular endothelial growth factor (anti-VEGF) agents and any signal transduction inhibitors (STIs)
- Uncontrolled hypertension
- Subjects with symptoms, signs, or history of brain metastases
- Any hemorrhage or bleeding event ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 4 weeks of start of study treatment
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 |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506)Subjects will receive regorafenib 160 mg od on days 4 to 10 and days 18 to 24 as four 40 mg coprecipitate tablets. In case of administration as a single agent during the study, regorafenib will be administered 160 mg od for 3 weeks on/1 week off. Each cycle consists of 28 days. | Drug | Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) |
| OxaliplatinOn day 1 and day 15 of each cycle, participants will receive 85 mg/m^2 oxaliplatin as a 2 hour i.v. infusion. | Drug | Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) |
| Folinic acidOn day 1 and day 15 of each cycle, participants will receive folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2 hour i.v. infusion. | Drug | Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) |
| 5-FU (mFOLFOX6)Participants will receive a 400 mg/m^2 5 FU i.v. bolus injection immediately followed by a 2400 mg/m^2 5 FU 46 hour i.v. infusion. | Drug | Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6) |
Primary outcome
Objective Response (OR)
Time frame: From start of treatment until 30 days after termination of study medication, an average of 47 weeks. Assessed every 8 weeks.
OR was defined as the best tumor response (confirmed complete response [CR] or partial response [PR]) observed by MRI or CT scan assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). Any pathological lymph nodes (whether target or non target) must have a reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing nontarget lesions and no appearance of new lesions.
5 secondary outcomes
Overall Survival (OS)
Time frame: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Progression-free Survival (PFS)
Time frame: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Disease Control (DC)
Time frame: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Duration of Response (DOR)
Time frame: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Duration of Stable Disease (DOSD)
Time frame: From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23493136Schultheis B, Folprecht G, Kuhlmann J, Ehrenberg R, Hacker UT, Kohne CH, Kornacker M, Boix O, Lettieri J, Krauss J, Fischer R, Hamann S, Strumberg D, Mross KB. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol. 2013 Jun;24(6):1560-7. doi: 10.1093/annonc/mdt056. Epub 2013 Mar 13.
- Click here to find information about studies related to Bayer Healthcare products conducted in EuropeLink provided by the sponsor.
Related trials for Colorectal Neoplasms
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
Bayer Study Director study director
Bayer
18 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib (Stivarga, BAY73-4506), Oxaliplatin and Folinic acid in people with Colorectal Neoplasms, run by Bayer at 18 sites in 7 countries.
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 8 inclusion and 6 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 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Germany, Belgium, Italy, Spain, Australia and 2 more countries. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 4 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response (OR) (time frame: From start of treatment until 30 days after termination of study medication, an average of 47 weeks. Assessed every 8 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01289821, which also lists 1 linked publication.
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 15 Mar 2017.