Advanced Chemorefractory Colorectal AdenocarcinomaPhase 2RegARd-CNCT01929616
Regorafenib Assessment in Refractory Advanced Colorectal Cancer(RegARd-C)
A Phase 2 study testing regorafenib in people with Advanced Chemorefractory Colorectal Adenocarcinoma, run by Jules Bordet Institute at 17 sites in Belgium.
Trial summary
The general objectives are to evaluate activity and the safety of regorafenib in a population of patients bearing advanced, refractory colorectal cancers and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Chemorefractory Colorectal Adenocarcinoma
- What is being tested?
- regorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 141 participants
- Where
- 17 sitesBelgium
- Study dates
- Aug 2013to 17 Jun 2019
- Phase
- Phase 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 proven colorectal adenocarcinoma that is metastatic or unresectable and for which standard treatments do not exist or are no longer effective.
- Age ≥ 18 years.
- Life expectancy of greater than 12 weeks.
- ECOG performance status ≤ 1.
- Participants must have normal organ and bone marrow function as defined below:
- Leukocytes >3,000/mcL,with an absolute neutrophil count >1,500/mcL, platelets >100,000/mcL, Hb >or=9g/dl.
Show all 15Show fewer
- Total bilirubin≤1.5×institutional ULN.
- AST/ALT/P-Alk levels ≤ 2.5 × institutional ULN (≤5x institutional ULN in case of liver metastatic involvement).
- Lipase ≤1.5 institutional ULN.
- coagulation tests ≤ 1.5 x institutional ULN.
- Creatinine ≤ 1.5× institutional ULN or creatinine clearance >30mL/min according to the Modified Diet in Renal Disease (MDRD) abbreviated formula.
- Women of childbearing potential and men must agree to use adequate contraception prior to study entry, until at least 3 months after the last study drug administration.
- Signed Written Informed Consent (IC).
- Presence of a previously collected or freshly obtained at the time of study entry frozen metastatic tumor biopsy in a FDG-PET targetable lesion.
- Presence of at least one metabolically measurable tumoral lesion on FDG PET-CT
Who cannot join
- Prior treatment with sorafenib or regorafenib
- Patients with previous cancer that is not disease-free for at least for 5 years prior to registration, EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Non-invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)].
- Participants who have had a major surgery, chemotherapy or radiotherapy within 4 weeks prior to entering the study.
- Unresolved toxicity higher than NCI-CTCAE (version 4.0) Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity ≤Grade 2.
- Participants receiving any experimental agents.
- Participants with known brain metastases.
Show all 24Show fewer
- Bleeding diathesis, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months.
- Any hemorrhage or bleeding event NCI-CTCAE v.4 Grade >or= 3 within 4 weeks prior to the start of study medication.
- Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association (NYHA)class> or=2), unstable angina pectoris, cardiac arrhythmia requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
- Uncontrolled hypertension.
- Patients with seizure disorder requiring medication.
- Any history of organ allograft.
- Pleural effusion or ascites affecting respiration.
- Uncontrolled diabetes.
- Non-healing wound, ulcer, or bone fracture.
- Known history of human immunodeficiency virus (HIV) infection, or active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
- Interstitial lung disease with ongoing signs and symptoms.
- Renal failure requiring hemo-or peritoneal dialysis.
- Dehydration NCI-CTCAE v.4 grade >1.
- Medical,psychological or social conditions that may interfere with the patient's ability to understand informed consent and participation in the study or evaluation of the study results.
- Known hypersensitivity to the study drug or excipients in the formulation.
- Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
- Pregnant or lactating women.
- Subjects unable to swallow oral medications.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Belgium17 sites
UZA
Antwerp, Edegem, 2650
Jules Bordet Institute
Brussels, 1000
Hopital Erasme
Brussels, 1070
Cliniques Universitaires Saint Luc
Brussels
Grand Hopital de Charleroi
Charleroi, 6000
UZ Ghent
Ghent
AZ groeninge
Kortrijk, 8500
Centre Hospitalier Universitaire de Liège
Liège, 4000
Clinique St Joseph
Liège, 4000
Centre hospitalier de Jolimont
Lobbes, 6540
CHU Ambroise Paré
Mons, 7000
Centre Hospitalier Régional de Namur
Namur, 5000
Clinique et Maternité Sainte Elisabeth
Namur, 5000
Clinique Saint Pierre
Ottignies, 1340
Hartziekenhuis Roeselare-Menen (HHRM)
Roeselare, 8800
AZ Turnhout
Turnhout, 2300
Cliniques Universitaires UCL de Mont-Godinne
Yvoir, 5530
About this study
Official title: Regorafenib Assessment in Refractory Advanced Colorectal Cancer
The general objectives are to evaluate activity and the safety of regorafenib in a population of patients bearing advanced, refractory colorectal cancers and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms.
Read the detailed description
The primary objective is to identify in a population of patients bearing advanced, refractory colorectal cancers, those who draw no benefit from treatment with regorafenib. There is no specific hypothesis underlying sample size and the study is therefore to be seen as exploratory.
Secondary objectives:
- To analyze PFS and response rate (RR) in relationship with the same covariates as for OS
- To assess regorafenib efficacy (OS, PFS, RR) and safety profile in this study population.
- To assess the Disease control rate (DCR = Complete response [CR] + partial response [PR] + stable disease [SD])
- To compare the relative benefit (OS, PFS) of regorafenib according to history of treatment with bevacizumab.
- Being tested
- regorafenib
- Keywords
- adenocarcinoma, colorectal,regorafenib
- Medical subject headings
- Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
regorafenibDrug
Also called stivarga (registred name)
Patients will receive 160 mg regorafenib 1/day 3 weeks out of 4.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | A treatment cycle is defined as a 4 weeks period. Regorafenib will be administered once a day orally at a dose of 160 mg (4 tablets of 40 mg), for 3 weeks. Receives: Drug: regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
Measured: 2 years from first patient in
Secondary outcomes (4)
Occurence of Adverse events
Assessment of safety will follow the WHO guidelines and classified according to NCI-CTCAE v. 4.0 and will be performed every 28 days until 28 days (safety follow up visit) after stopping therapy. Reasons for stopping therapy may include progression of disease or unbearable toxicities, or patient's decision.
Measured: Every 28 days till 28 days after stopping therapy. An average of 2 months is expected.
Evaluation of tumour response
RECIST 1.1-based radiological assessment (CT or MRI) will be made every 2 cycles, starting at day 28 of the second cycle till demonstration of progressive disease. An average of 2 months is expected.
Measured: Every 2 months till progression of the disease. An average of 2 months is expected.
Metabolic response assessed by FDG PET
FDGPET will be done twice during the study course : at baseline (at day 0, before treatment begin) and after 2 weeks.
Measured: 2 FDGPET will be perfomed : at Baseline (day 0) and at D14
Molecular aberrations
Genetic, epigenetic and molecular aberrations will be investigated using gene expression profiling, RNA and exome sequencing, and methylation profiling on the tumor biopsies and repeated blood samples collected during the trial. The relationship between the molecular aberrations,the patient's outcome (PFS, OS) and with metabolic response after treatment with regorafenib will be studied.
Measured: at day 0 (before treatment begins) and at D14, then repeated every 2 months until progression. An average of 2 months is expected.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2013 (estimated)
- Study startAug 2013
- Primary completion13 May 2016
- Study completion17 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Chemorefractory Colorectal AdenocarcinomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jules Bordet Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alain Hendlisz, MD, Study chair, Jules Bordet Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01929616
- Sponsor's protocol ID
- 2012-005655-16 EUDRACT
- Acronym
- RegARd-C
- Status last verified
- Mar 2017
- First submitted
- 28 Jul 2013
- Last updated
- 25 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Charette N, Vandeputte C, Ameye L, Bogaert CV, Krygier J, Guiot T, Deleporte A, Delaunoit T, Geboes K, Van Laethem JL, Peeters M, Demolin G, Holbrechts S, Flamen P, Paesmans M, Hendlisz A. Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials. BMC Cancer. 2019 Feb 12;19(1):134. doi: 10.1186/s12885-019-5319-8.
PubMed 30744591Hendlisz A, Deleporte A, Vandeputte C, Charette N, Paesmans M, Guiot T, Garcia C, Flamen P. Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol. BMJ Open. 2015 Mar 9;5(3):e007189. doi: 10.1136/bmjopen-2014-007189.
PubMed 25753361
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regorafenib Assessment in Refractory Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01929616
- Acronym / sponsor ID
- RegARd-C / 2012-005655-16 EUDRACT
- Keywords
- adenocarcinoma, colorectal,regorafenib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Jules Bordet InstituteUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- 13 May 2016 (actual)
- Study completion
- 17 Jun 2019 (actual)
- First posted
- 28 Aug 2013 (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 general objectives are to evaluate activity and the safety of regorafenib in a population of patients bearing advanced, refractory colorectal cancers and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms.
Detailed description
The primary objective is to identify in a population of patients bearing advanced, refractory colorectal cancers, those who draw no benefit from treatment with regorafenib. There is no specific hypothesis underlying sample size and the study is therefore to be seen as exploratory.
Secondary objectives:
- To analyze PFS and response rate (RR) in relationship with the same covariates as for OS
- To assess regorafenib efficacy (OS, PFS, RR) and safety profile in this study population.
- To assess the Disease control rate (DCR = Complete response [CR] + partial response [PR] + stable disease [SD])
- To compare the relative benefit (OS, PFS) of regorafenib according to history of treatment with bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: regorafenibA treatment cycle is defined as a 4 weeks period. Regorafenib will be administered once a day orally at a dose of 160 mg (4 tablets of 40 mg), for 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically proven colorectal adenocarcinoma that is metastatic or unresectable and for which standard treatments do not exist or are no longer effective.
- Age ≥ 18 years.
- Life expectancy of greater than 12 weeks.
- ECOG performance status ≤ 1.
- Participants must have normal organ and bone marrow function as defined below:
Key exclusion criteria (24 listed)
- Prior treatment with sorafenib or regorafenib
- Patients with previous cancer that is not disease-free for at least for 5 years prior to registration, EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Non-invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)].
- Participants who have had a major surgery, chemotherapy or radiotherapy within 4 weeks prior to entering the study.
- Unresolved toxicity higher than NCI-CTCAE (version 4.0) Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity ≤Grade 2.
- Participants receiving any experimental agents.
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 |
|---|---|---|
| regorafenibAlso: stivarga (registred name)Patients will receive 160 mg regorafenib 1/day 3 weeks out of 4. | Drug | Regorafenib |
Primary outcome
Overall survival (OS)
Time frame: 2 years from first patient in
4 secondary outcomes
Occurence of Adverse events
Time frame: Every 28 days till 28 days after stopping therapy. An average of 2 months is expected.
Evaluation of tumour response
Time frame: Every 2 months till progression of the disease. An average of 2 months is expected.
Metabolic response assessed by FDG PET
Time frame: 2 FDGPET will be perfomed : at Baseline (day 0) and at D14
Molecular aberrations
Time frame: at day 0 (before treatment begins) and at D14, then repeated every 2 months until progression. An average of 2 months is expected.
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 25 Jun 2019.
- Derived from this study: PubMed 30744591Charette N, Vandeputte C, Ameye L, Bogaert CV, Krygier J, Guiot T, Deleporte A, Delaunoit T, Geboes K, Van Laethem JL, Peeters M, Demolin G, Holbrechts S, Flamen P, Paesmans M, Hendlisz A. Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials. BMC Cancer. 2019 Feb 12;19(1):134. doi: 10.1186/s12885-019-5319-8.
- Derived from this study: PubMed 25753361Hendlisz A, Deleporte A, Vandeputte C, Charette N, Paesmans M, Guiot T, Garcia C, Flamen P. Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol. BMJ Open. 2015 Mar 9;5(3):e007189. doi: 10.1136/bmjopen-2014-007189.
Related trials for Advanced Chemorefractory Colorectal Adenocarcinoma
RecruitingPhase 2
CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors
Advanced Biliary Tract Carcinoma, Advanced Colorectal Carcinoma
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.
Alain Hendlisz, MD study chair
Jules Bordet Institute
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing regorafenib in people with Advanced Chemorefractory Colorectal Adenocarcinoma, run by Jules Bordet Institute at 17 sites in Belgium.
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 15 inclusion and 24 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 25 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Belgium. 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?
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?
Overall survival (OS) (time frame: 2 years from first patient in). 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 NCT01929616, which also lists 2 linked publications.
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 25 Jun 2019.