Metastatic Colorectal CancerPhase 2RE-ARRANGENCT02835924
Study Comparing Different Dose Approaches of Induction Treatment of Regorafenib in MCRC
A Phase 2 study testing Regorafenib in people with Metastatic Colorectal Cancer, run by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) at 1 site in Spain.
Trial summary
The purpose of this study is to assess the safety and tolerability of different dose-escalation approaches of regorafenib in mCRC patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Regorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 299 participants
- Where
- 1 siteSpain
- Study dates
- Jul 2016to Sep 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
- Signed informed consent (IC) obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
- Male or female subjects 18 years of age.
- Life expectancy of at least 3 months.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
- Measurable metastatic stage IV disease with at least 1 measurable metastatic lesion following RECIST criteria v 1.1.
- Subjects with metastatic colorectal cancer (Stage IV).
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- Progression during or within 3 months following the last administration of approved standard therapies which must include fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF and an anti-EGFR (if RAS WT)
- Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy
- Subjects who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated with oxaliplatin-based therapy to be eligible. Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed into the study
- ECOG Performance Status of 0 or 1(within 14 days prior to the initiation of study treatment)
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
- Total bilirubin =1.5 x the upper limit of normal (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (5 x ULN for subjects with liver involvement of their cancer).
- Alkaline phosphatase limit = 2.5 x ULN (5 x ULN for subjects with liver and/or bone involvement of their cancer).
- Lipase = 1.5 x the ULN.
- Serum creatinine 1.5 x the ULN or = 30 mL/min as calculated using the Cockcroft-Gault equation.
- Platelet count >100000/mm3, hemoglobin >9 g/dL, absolute neutrophil count (ANC) >1500/mm3.
- International normalized ratio (INR)/ Partial thromboplastin time (PTT) 1.5 x ULN. (Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard.
- Blood transfusion to meet the inclusion criteria will not be allowed.
- Women of childbearing potential and men must agree to use adequate contraception before entering the program until at least 8 weeks after the last study drug administration. The investigator or a designated associate is requested to advise the subject on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care. Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment.
Who cannot join
- Prior treatment with regorafenib.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug
- Pregnant or breast-feeding subjects:
- Congestive heart failure = New York Heart Association (NYHA) class 2.
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
- Myocardial infarction less than 6 months before start of study drug.
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- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
- Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure >90 mmHg despite optimal medical management).
- Arterial or venous thromboembolism within 6 months prior to randomization.
- Pleural effusion or ascites that causes respiratory compromise (CTCAE Grade 2 dyspnea).
- Ongoing infection > Grade 2 CTCAE v. 4.0.
- Known history of human immunodeficiency virus (HIV) infection.
- Known history of active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
- Subjects with seizure disorder requiring medication.
- History of organ allograft.
- Subjects with evidence or history of any bleeding diathesis, irrespective of severity.
- Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of study medication.
- Non-healing wound, ulcer, or bone fracture.
- Renal failure requiring hemo-or peritoneal dialysis.
- Dehydration CTCAE v. 4.0 Grade = 1.
- Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
- Any illness or medical conditions that are unstable or could jeopardize the safety of the subject and his/her compliance in the study.
- Interstitial lung disease with ongoing signs and symptoms
- Persistent proteinuria of CTCAE Grade 3 (>3.5g/24 hours).
- Subjects unable to swallow oral medications.
- Any malabsorption condition.
- Unresolved toxicity higher than CTCAE (v. 4.0) > Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neurotoxicity > Grade 2.
- Subjects treated with strong CYP3A4 inhibitors or inducers (refer to appendix 8 and to section 6.3.8. Prohibited concomitant medication).
- Subjects receiving G-CSF within 3 weeks prior to signing the ICF
- Concomitant participation or participation within the last 30 days in another clinical trial
- Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 4 weeks (or within 6 weeks for mitomycin C) before starting to receive study medication.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Spanish Cooperative Group for the Treatment of Digestive Tumors
Madrid, 28007
About this study
Official title: A Randomized Phase 2 Study Comparing Different Dose Approaches of Induction Treatment (First Cycle) of Regorafenib in Metastatic Colorectal Cancer (mCRC) Patients
The purpose of this study is to assess the safety and tolerability of different dose-escalation approaches of regorafenib in mCRC patients.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Regorafenib
- Keywords
- regorafenib, metastatic colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | 160 mg/day 3w on/1w off Receives: Drug: Regorafenib |
| Arm B | Experimental | 120 mg/day 3w on/1w off 1st cycle; 160 mg/day 3w on/1w off 2nd cycle on Receives: Drug: Regorafenib |
| Arm C | Experimental | 160 mg/day 1w on/1w off 1st cycle; 160 mg/day 3w on/1w off 2nd cycle on Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with G3/G4 treatment-related AEs in each arm according to CTCAE v4.03 criteria.
Measured: 30 months
Secondary outcomes (7)
Percentage of total administrated dose over the planned dose accomplished in each arm.
Measured: 30 months
Dose intensity during the whole treatment.
Measured: 30 months
Dose intensity during first two cycles.
Measured: 2 months
Disease control rate (DCR)
Measured: 30 months
Progression-free survival (PFS)
Measured: 30 months
Time to treatment failure (TTF)
Measured: 30 months
Overall survival (OS)
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionSep 2018
- Study completionSep 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 Metastatic Colorectal CancerStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 299 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Guillem Argiles, Study chair, Hospital Universitary Vall d'HebronJosep Mª Tabernero, MD-PhD, Study chair, Hospital Universitary Vall d'Hebron
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02835924
- Sponsor's protocol ID
- TTD-16-01
- Acronym
- RE-ARRANGE
- Status last verified
- Mar 2020
- First submitted
- 8 Jul 2016
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Argiles G, Mulet N, Valladares-Ayerbes M, Vieitez JM, Gravalos C, Garcia-Alfonso P, Santos C, Tobena M, Garcia-Paredes B, Benavides M, Cano MT, Loupakis F, Rodriguez-Garrote M, Rivera F, Goldberg RM, Cremolini C, Bennouna J, Ciardiello F, Tabernero JM, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and UNICANCER GI; The, REARRANGE investigators; Principal investigator; Argiles G, Tabernero J; Steering Committee; Investigators. A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial). Eur J Cancer. 2022 Dec;177:154-163. doi: 10.1016/j.ejca.2022.09.037. Epub 2022 Oct 14.
PubMed 36335783Weinberg BA, Hartley ML, Salem ME. Precision Medicine in Metastatic Colorectal Cancer: Relevant Carcinogenic Pathways and Targets-PART 2: Approaches Beyond First-Line Therapy, and Novel Biologic Agents Under Investigation. Oncology (Williston Park). 2017 Jul 15;31(7):573-80.
PubMed 28712102
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2 Study Comparing Different Dose Approaches of Induction Treatment (First Cycle) of Regorafenib in Metastatic Colorectal Cancer (mCRC) Patients
- ClinicalTrials.gov ID
- NCT02835924
- Acronym / sponsor ID
- RE-ARRANGE / TTD-16-01
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- regorafenib, metastatic colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 299 participants (actual)
- Lead sponsor
- Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)University, hospital or other
- Collaborators
- Bayer
- Study start
- Jul 2016 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 18 Jul 2016 (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 assess the safety and tolerability of different dose-escalation approaches of regorafenib in mCRC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Regorafenib160 mg/day 3w on/1w off |
| Arm B | Experimental | Drug: Regorafenib120 mg/day 3w on/1w off 1st cycle; 160 mg/day 3w on/1w off 2nd cycle on |
| Arm C | Experimental | Drug: Regorafenib160 mg/day 1w on/1w off 1st cycle; 160 mg/day 3w on/1w off 2nd cycle on |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Signed informed consent (IC) obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
- Male or female subjects 18 years of age.
- Life expectancy of at least 3 months.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
- Measurable metastatic stage IV disease with at least 1 measurable metastatic lesion following RECIST criteria v 1.1.
Key exclusion criteria (32 listed)
- Prior treatment with regorafenib.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug
- Pregnant or breast-feeding subjects:
- Congestive heart failure = New York Heart Association (NYHA) class 2.
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
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 | Drug | Arm A, Arm B, Arm C |
Primary outcome
Percentage of patients with G3/G4 treatment-related AEs in each arm according to CTCAE v4.03 criteria.
Time frame: 30 months
7 secondary outcomes
Percentage of total administrated dose over the planned dose accomplished in each arm.
Time frame: 30 months
Dose intensity during the whole treatment.
Time frame: 30 months
Dose intensity during first two cycles.
Time frame: 2 months
Disease control rate (DCR)
Time frame: 30 months
Progression-free survival (PFS)
Time frame: 30 months
Time to treatment failure (TTF)
Time frame: 30 months
Overall survival (OS)
Time frame: 30 months
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 10 Mar 2020.
- Derived from this study: PubMed 36335783Argiles G, Mulet N, Valladares-Ayerbes M, Vieitez JM, Gravalos C, Garcia-Alfonso P, Santos C, Tobena M, Garcia-Paredes B, Benavides M, Cano MT, Loupakis F, Rodriguez-Garrote M, Rivera F, Goldberg RM, Cremolini C, Bennouna J, Ciardiello F, Tabernero JM, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and UNICANCER GI; The, REARRANGE investigators; Principal investigator; Argiles G, Tabernero J; Steering Committee; Investigators. A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial). Eur J Cancer. 2022 Dec;177:154-163. doi: 10.1016/j.ejca.2022.09.037. Epub 2022 Oct 14.
- Derived from this study: PubMed 28712102Weinberg BA, Hartley ML, Salem ME. Precision Medicine in Metastatic Colorectal Cancer: Relevant Carcinogenic Pathways and Targets-PART 2: Approaches Beyond First-Line Therapy, and Novel Biologic Agents Under Investigation. Oncology (Williston Park). 2017 Jul 15;31(7):573-80.
- Individual participant dataSharing planned: No
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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.
Guillem Argiles study chair
Hospital Universitary Vall d'Hebron
Josep Mª Tabernero, MD-PhD study chair
Hospital Universitary Vall d'Hebron
1 site 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 Metastatic Colorectal Cancer, run by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) at 1 site in Spain.
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 20 inclusion and 32 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 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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?
Percentage of patients with G3/G4 treatment-related AEs in each arm according to CTCAE v4.03 criteria. (time frame: 30 months). 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 NCT02835924, 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 10 Mar 2020.