Rectal CancerPhase 1RECAPNCT02910843
Neoadjuvant Treatment With Regorafenib and Capecitabine Combined With Radiotherapy in Locally Advanced Rectal Cancer
A Phase 1 study testing Regorafenib, Capecitabine and Radiotherapy in people with Rectal Cancer, run by Swiss Cancer Institute at 7 sites in Switzerland.
Trial summary
Despite treatment of locally advanced rectal cancer relapses are frequent. Several attempts to improve these results with therapy intensification have shown modest effect on disease free survival (DFS) and overall survival (OS). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Regorafenib, Capecitabine and Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 7 sitesSwitzerland
- Study dates
- 22 Feb 2017to 31 Dec 2021
- Phase
- Phase 1
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent according to Swiss law and ICH/GCP regulations before any trial specific procedures.
- Histologically confirmed and clinically advanced adenocarcinoma. pStage 2 and 3 according AJCC 2012, mrT3/4 N0, mrTx N1-2 cM0 (assessed by mandatory CT scan thorax/abdomen, MRI pelvis). TNM classification; recommended MRI quality assurance.
- Tumor is located in the lower and middle rectum (caudal end is defined at maximum of 12 cm from anal verge measured by endoscopy).
- A multi-disciplinary tumor board recommends neoadjuvant radio-chemotherapy and surgery.
- No DPD deficiency (Dihydro-pyrimidine-dehydrogenase DPD deficiency test mandatory). Carrier status of a predefined risk allele of the dihydro-pyrimidine-dehydrogenase gene (DPYD), defined as the presence of at least one of the following mutations: c.1679T>G, c.1905+1G>A, c.2846A>T, c.1129-5923C>G.
- Age 18 to 75 years.
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- WHO performance status 0-1.
- Adequate bone marrow function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 100 g/L.
- Adequate hepatic and pancreatic function: bilirubin ≤ 1.5 x ULN, AST/ALT/AP ≤ 2.5 x ULN, Lipase ≤ 1.5 x the ULN.
- Adequate renal function (calculated creatinine clearance > 50 mL/min, according to the formula of Cockcroft-Gault).
- INR ≤ 1.5 or PTT ≤ 1.5 x ULN (patients who are being therapeutically anticoagulated are not allowed to participate in the trial). If anti coagulation is indicated during trial treatment, low molecular weight heparin must be used.
- Women with child-bearing potential are using effective contraception, are not pregnant and agree not to become pregnant during trial treatment and during the 8 weeks thereafter. A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential.
- Men agree to use effective contraception during trial treatment and 8 weeks thereafter.
Who cannot join
- History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
- Concurrent or recent (within 30 days of registration) treatment with any other experimental drug.
- Any prior treatment for rectal cancer.
- Major surgery or significant traumatic injury within 28 days before registration (colostomy accepted).
- Concomitant strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) within 28 days or 5 drug half-lives (if drug half-life in patients is known), whichever is shorter, before start of trial treatment (see http://medicine.iupui.edu/).
- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA II-IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation (QTc interval >460 msec), uncontrolled hypertension (sustained systolic blood pressure > 150 mm Hg and/or diastolic > 100 mm Hg despite antihypertensive therapy).
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- Patients with evidence or history of any bleeding diathesis, irrespective of severity.
- Any hemorrhage or bleeding event ≥ Grade 3, NCI-CTCAE v4.03 within 4 weeks prior to the start of trial medication.
- Significant proteinuria: Positive dipstick 2+ and greater if proteinuria ≥ 3.5g/24 h measured by urine protein-creatinine ratio is confirmed (≥ Grade 3, NCI-CTCAE v4.0).
- Patients with known hepatopathy as cirrhosis or diseases like Morbus Gilbert Meulengracht.
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment.
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
- History of organ allografts.
- Known hypersensitivity to any of the trial drugs, trial drug classes, or excipients in the formulation.
- Breast-feeding patients.
- Any concomitant drugs contraindicated for use with the trial drugs according to the Swissmedic approved product information.
- Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Switzerland7 sites
St. Claraspital Basel
Basel, 4016
Universitätsspital Basel
Basel, 4031
Inselspital Bern
Bern, 3010
Kantonsspital Graubünden
Chur, 7000
Kantonsspital Luzern
Lucerne, 6000
Kantonsspital St. Gallen
Sankt Gallen, 9007
UniversitätsSpital Zürich
Zurich, 8091
About this study
Official title: Neoadjuvant Treatment With Regorafenib and Capecitabine Combined With Radiotherapy in Locally Advanced Rectal Cancer. A Multicenter Phase Ib Trial (RECAP)
Despite treatment of locally advanced rectal cancer relapses are frequent. Several attempts to improve these results with therapy intensification have shown modest effect on disease free survival (DFS) and overall survival (OS). Recent studies with addition of sorafenib and cediranib revealed promising effect on tumor response with acceptable toxicity. Regorafenib is a multi tyrosine kinase inhibitor (TKI) with a broad mechanism of action. Therefore this trial investigates if similar results can be achieved as with sorafenib or cediranib.
Read the detailed description
Despite treatment of locally advanced rectal cancer relapses are frequent. Several attempts to improve these results with therapy intensification have shown modest effect on disease free survival (DFS) and overall survival (OS). Recent studies with addition of sorafenib and cediranib revealed promising effect on tumor response with acceptable toxicity. Regorafenib is a multi tyrosine kinase inhibitor (TKI) with a broad mechanism of action. Therefore this trial investigates if similar results can be achieved as with sorafenib or cediranib.
The objective of the dose escalation part is to determinate safety, tolerability and the recommended dose. The objective of the expansion cohort is to assess the efficacy and to further characterize safety and tolerability of the therapy.
- Conditions
- Rectal Cancer
- Being tested
- Regorafenib, Capecitabine, Radiotherapy, Surgery
- Keywords
- rectal cancer, Neoadjuvant treatment, Regorafenib, Capecitabine, locally advanced rectal cancer, Phase Ib trial
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called BAY 73-4506
- Regorafenib dosel level 1-3: day 1 to 14 and day 22 to 35 (2 weeks on 1 week off, 2 weeks on, including Saturday and Sunday) at a daily dose according to the escalation table.
- Regorafenib dosel level -1: day 1 to 5, day 8 to 12, day 22 to 26 and day 29 to 33 (5 days on and 2 days off during week 1, 2, 4 and 5; week 3 off) at a daily dose according to the escalation table.
CapecitabineDrug
Also called XELODA
- Capecitabine: day 1 to 38 (5 weeks and 3 days, including Saturday and Sunday) according to dose escalation table. The intake stops in the evening of the last day of RT.
RadiotherapyRadiation
Monday through Friday for 5 weeks and 3 days (d1-38) starting on day 1 (daily fraction 1.8 Gy, final dose 50.4 Gy).
SurgeryProcedure or surgery
6-12 weeks (± 1 week) after radio-chemotherapy (RCT) has been completed (42-84 days after last day of RCT).
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib & Capecitabine | Experimental | * Regorafenib dose level 1-3: day 1 to 14 and day 22 to 35 (2 weeks on 1 week off, 2 weeks on, including Saturday and Sunday) at a daily dose according to the escalation table.
* Regorafenib dose level -1: day 1 to 5, day 8 to 12, day 22 to 26 and day 29 to 33 (5 days on and 2 days off during week 1, 2, 4 and 5; week 3 off) at a daily dose according to the escalation table.
* Capecitabine: day 1 to 38 (5 weeks and 3 days, including Saturday and Sunday) according to dose escalation table. The intake stops in the evening of the last day of RT.
* External beam Radiotherapy
* Surgery Receives: Drug: Regorafenib; Drug: Capecitabine; Radiation: Radiotherapy; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLTs)
In the dose escalation part the dose limiting toxicity (DLTs) is observed during and up to 4 weeks after the last administration of RCT.
Measured: up to 4 weeks after the last administration of RCT
Pathological near complete or complete tumor response (npCR or pCR)
In the dose escalation part the pathological near complete or complete tumor response (npCR or pCR) is specified.
Measured: up to 2 months after end of treatment
Secondary outcomes (6)
Quality of the mesorectal excision including details of the circumferential resection margin (CRM)/surface
Quality of the mesorectal excision including details of the circumferential resection margin (CRM)/surface according to Nagtegaal.
Measured: up to 2 months after end of treatment
Sphincter preservation
Sphincter preservation is defined as preservation of the rectal sphincter or part of it.
Measured: up to 2 months after end of treatment
Pathological response
Dworak tumor regression grading (TRG) system.
Measured: up to 2 months after end of treatment
Circumferential resection margin (CRM) status
Negative (clear) circumferential margins are defined by an invasion front which is at a > 1mm distance from the lateral resection margin; circumferential resection margins of ≤ 1 mm are considered positive (involved).
CRM negative (clear) ≤ 1mm and CRM positive (involved) ≤ 1mm.
Measured: up to 2 months after end of treatment
Downstaging of primary tumor and/or lymph nodes (comparison between mrT/N and ypT/N)
Downstaging of primary tumor and/or lymph nodes (comparison between mrT/N and ypT/N)
Measured: up to 2 months after end of treatment
Postoperative complications
Surgical complications within 8 weeks after surgery. A surgical local complication is defined as either:
- insufficiency of anastomosis
- fistula
- severe local infection requiring antibiotics
- bladder dysfunction
- erectile dysfunction
- additional interventions / operation needed (e.g. drainage of hematoma/abscess)
Measured: within 8 weeks after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study start22 Feb 2017
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Why it stopped: due to structural financial deficit of SAKK
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sara Bastian, MD, Study chair, Kantonsspital Graubünden, Chur
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02910843
- Sponsor's protocol ID
- SAKK 41/16 - RECAP
- Acronym
- RECAP
- Status last verified
- Jan 2023
- First submitted
- 14 Sep 2016
- Last updated
- 10 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Treatment With Regorafenib and Capecitabine Combined With Radiotherapy in Locally Advanced Rectal Cancer. A Multicenter Phase Ib Trial (RECAP)
- ClinicalTrials.gov ID
- NCT02910843
- Acronym / sponsor ID
- RECAP / SAKK 41/16 - RECAP
- Conditions
- Rectal Cancer
- Keywords
- rectal cancer, Neoadjuvant treatment, Regorafenib, Capecitabine, locally advanced rectal cancer, Phase Ib trial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to structural financial deficit of SAKK
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Swiss Cancer InstituteUniversity, hospital or other
- Study start
- 22 Feb 2017 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 22 Sep 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.
Despite treatment of locally advanced rectal cancer relapses are frequent. Several attempts to improve these results with therapy intensification have shown modest effect on disease free survival (DFS) and overall survival (OS). Recent studies with addition of sorafenib and cediranib revealed promising effect on tumor response with acceptable toxicity. Regorafenib is a multi tyrosine kinase inhibitor (TKI) with a broad mechanism of action. Therefore this trial investigates if similar results can be achieved as with sorafenib or cediranib.
Detailed description
Despite treatment of locally advanced rectal cancer relapses are frequent. Several attempts to improve these results with therapy intensification have shown modest effect on disease free survival (DFS) and overall survival (OS). Recent studies with addition of sorafenib and cediranib revealed promising effect on tumor response with acceptable toxicity. Regorafenib is a multi tyrosine kinase inhibitor (TKI) with a broad mechanism of action. Therefore this trial investigates if similar results can be achieved as with sorafenib or cediranib.
The objective of the dose escalation part is to determinate safety, tolerability and the recommended dose. The objective of the expansion cohort is to assess the efficacy and to further characterize safety and tolerability of the therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib & Capecitabine | Experimental | Drug: Regorafenib, Drug: Capecitabine, Radiation: Radiotherapy, Procedure: Surgery* Regorafenib dose level 1-3: day 1 to 14 and day 22 to 35 (2 weeks on 1 week off, 2 weeks on, including Saturday and Sunday) at a daily dose according to the escalation table. * Regorafenib dose level -1: day 1 to 5, day 8 to 12, day 22 to 26 and day 29 to 33 (5 days on and 2 days off during week 1, 2, 4 and 5; week 3 off) at a daily dose according to the escalation table. * Capecitabine: day 1 to 38 (5 weeks and 3 days, including Saturday and Sunday) according to dose escalation table. The intake stops in the evening of the last day of RT. * External beam Radiotherapy * Surgery |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent according to Swiss law and ICH/GCP regulations before any trial specific procedures.
- Histologically confirmed and clinically advanced adenocarcinoma. pStage 2 and 3 according AJCC 2012, mrT3/4 N0, mrTx N1-2 cM0 (assessed by mandatory CT scan thorax/abdomen, MRI pelvis). TNM classification; recommended MRI quality assurance.
- Tumor is located in the lower and middle rectum (caudal end is defined at maximum of 12 cm from anal verge measured by endoscopy).
- A multi-disciplinary tumor board recommends neoadjuvant radio-chemotherapy and surgery.
- No DPD deficiency (Dihydro-pyrimidine-dehydrogenase DPD deficiency test mandatory). Carrier status of a predefined risk allele of the dihydro-pyrimidine-dehydrogenase gene (DPYD), defined as the presence of at least one of the following mutations: c.1679T>G, c.1905+1G>A, c.2846A>T, c.1129-5923C>G.
Key exclusion criteria (18 listed)
- History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
- Concurrent or recent (within 30 days of registration) treatment with any other experimental drug.
- Any prior treatment for rectal cancer.
- Major surgery or significant traumatic injury within 28 days before registration (colostomy accepted).
- Concomitant strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) within 28 days or 5 drug half-lives (if drug half-life in patients is known), whichever is shorter, before start of trial treatment (see http://medicine.iupui.edu/).
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: BAY 73-4506* Regorafenib dosel level 1-3: day 1 to 14 and day 22 to 35 (2 weeks on 1 week off, 2 weeks on, including Saturday and Sunday) at a daily dose according to the escalation table. * Regorafenib dosel level -1: day 1 to 5, day 8 to 12, day 22 to 26 and day 29 to 33 (5 days on and 2 days off during week 1, 2, 4 and 5; week 3 off) at a daily dose according to the escalation table. | Drug | Regorafenib & Capecitabine |
| CapecitabineAlso: XELODA• Capecitabine: day 1 to 38 (5 weeks and 3 days, including Saturday and Sunday) according to dose escalation table. The intake stops in the evening of the last day of RT. | Drug | Regorafenib & Capecitabine |
| RadiotherapyMonday through Friday for 5 weeks and 3 days (d1-38) starting on day 1 (daily fraction 1.8 Gy, final dose 50.4 Gy). | Radiation | Regorafenib & Capecitabine |
| Surgery6-12 weeks (± 1 week) after radio-chemotherapy (RCT) has been completed (42-84 days after last day of RCT). | Procedure or surgery | Regorafenib & Capecitabine |
Primary outcome
Dose limiting toxicity (DLTs)
Time frame: up to 4 weeks after the last administration of RCT
In the dose escalation part the dose limiting toxicity (DLTs) is observed during and up to 4 weeks after the last administration of RCT.
Pathological near complete or complete tumor response (npCR or pCR)
Time frame: up to 2 months after end of treatment
In the dose escalation part the pathological near complete or complete tumor response (npCR or pCR) is specified.
6 secondary outcomes
Quality of the mesorectal excision including details of the circumferential resection margin (CRM)/surface
Time frame: up to 2 months after end of treatment
Sphincter preservation
Time frame: up to 2 months after end of treatment
Pathological response
Time frame: up to 2 months after end of treatment
Circumferential resection margin (CRM) status
Time frame: up to 2 months after end of treatment
Downstaging of primary tumor and/or lymph nodes (comparison between mrT/N and ypT/N)
Time frame: up to 2 months after end of treatment
Postoperative complications
Time frame: within 8 weeks after surgery
Results and safety
The study was stopped early (reason given: due to structural financial deficit of SAKK). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
- Individual participant dataSharing planned: No
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Neoplasms
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.
Sara Bastian, MD study chair
Kantonsspital Graubünden, Chur
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Regorafenib, Capecitabine and Radiotherapy in people with Rectal Cancer, run by Swiss Cancer Institute at 7 sites in Switzerland.
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 18 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: stopped early, as of the sponsor's last update on 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Switzerland. 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 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.
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 was stopped early (reason given: due to structural financial deficit of SAKK). Results are not available in the source record.
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?
Dose limiting toxicity (DLTs) (time frame: up to 4 weeks after the last administration of RCT). 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 10 Jan 2023; AzTrials last refreshed its copy on 8 Nov 2026.