Recurrent Rectal CancerPhase 3PelvEx IINCT04389086
Induction Chemotherapy for Locally Recurrent Rectal Cancer
A Phase 3 study testing Combination drug, Chemoradiotherapy and Surgery locally recurrent rectal cancer in people with Recurrent Rectal Cancer, run by Catharina Ziekenhuis Eindhoven at 14 sites in 5 countries.
Trial summary
This is a multicentre, open-label, parallel arms, phase IIII study that randomises patients with locally recurrent rectal cancer in a 1:1 ratio to receive either induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Rectal Cancer
- What is being tested?
- Combination drug, Chemoradiotherapy and Surgery locally recurrent rectal cancer
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 364 participants
- Where
- 14 sitesin 5 countries
- Study dates
- 13 Nov 2020to 1 Mar 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- 18 years or older
- Confirmed locally recurrent rectal cancer after total or partial mesorectal resection for rectal or distal sigmoidal cancer either by histopathology ór clinically proven (evidence on imaging in combination with clinical findings, with consensus in MDT)
- Resectable disease determined by magnetic resonance imaging (MRI) or deemed resectable after neoadjuvant treatment with chemoradiotherapy.
- WHO performance score 0-1
- Written informed consent
Who cannot join
- Radiological evidence of metastatic disease (e.g. liver, lung) at time of randomisation or in the six months prior to randomisation.
- Known homozygous DPD deficiency
- Any chemotherapy in the past 6 months.
- Any contraindication for the planned chemotherapy, as determined by the medical oncologist.
- Radiotherapy in the past 6 months for primary rectal cancer.
- Any contraindication for the planned chemoradiotherapy, as determined by the medical oncologist and/or radiation oncologist.
- Any contraindication for surgery, as determined by the surgeon and/or anaesthesiologist.
- Concurrent malignancies that interfere with the planned study treatment or the prognosis of resected LRRC.
Trial locations and contacts
14 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
14 sites in 5 countries
Netherlands8 sites, 8 recruiting
- Recruiting
Amsterdam UMC
Amsterdam
Miranda Kusters, MD, PhD
- Recruiting
Antoni van Leeuwenhoek
Amsterdam
Arend Aalbers, MD, PhD
- Recruiting
Catharina Hospital
Eindhoven, 5623EJ
Stefi Nordkamp, MD, 0031 40 2398858, pelvex2@catharinaziekenhuis.nl
Pim Burger, MD, PhD, pim.burger@catharinaziekenhuis.nl
- Recruiting
University Medical Centre Groningen
Groningen
Klaas Havenga, MD, PhD
- Recruiting
Leids University Medical Centre
Leiden
Fabian Holman, Md, PhD
- Recruiting
Haaglanden Medical Centre
Leidschendam
Andreas Marinelli, MD, PhD
- Recruiting
Maastricht University Medical Centre
Maastricht
Jarno Melenhorst, MD, PhD
- Recruiting
Erasmus Medical Centre
Rotterdam
Cornelis Verhoef, MD, PhD
Sweden3 sites, 3 recruiting
- Not yet recruiting
Sahlgrenska Universitetssjukhuset
Gothenburg
Eva Angenete, MD, PhD
Sofia Heyman, MD, PhD
- Not yet recruiting
Skåne Universitetssjukhuset
Malmö
Pamela Buchwald, MD, PhD
- Not yet recruiting
Karolinska Universitetssjukhuset
Stockholm
Henrik Iversen, MD, PhD
Belgium1 site, 1 recruiting
- Not yet recruiting
UZ Gent
Ghent
Gabrielle van Ramshorst, MD, PhD
Norway1 site, 1 recruiting
- Not yet recruiting
Oslo Universitetssykehus
Oslo
Marianne Guren, MD, PhD
Portugal1 site, 1 recruiting
- Not yet recruiting
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.
Lisbon
João Maciel, MD, PhD
About this study
Official title: Multicentre, Open-label, Randomised, Controlled, Parallel Arms Clinical Trial of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone as Neoadjuvant Treatment for Locally Recurrent Rectal Cancer - PelvEx II
This is a multicentre, open-label, parallel arms, phase IIII study that randomises patients with locally recurrent rectal cancer in a 1:1 ratio to receive either induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm)
- Conditions
- Recurrent Rectal Cancer
- Being tested
- Combination drug, Chemoradiotherapy, Surgery locally recurrent rectal cancer
- Keywords
- Locally recurrent rectal cancer, Neoadjuvant therapy, Induction chemotherapy, Resection margin
- Medical subject headings
- Rectal Neoplasms, Margins of Excision
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination drugDrug
Also called CAPOX, FOLFOX, FOLFIRI
Induction chemotherapy consists of either three three-weekly cycles of CAPOX (oxaliplatin 130 mg/m2 BSA IV + capecitabine 1000 mg/m2 BSA, orally, twice daily) or four two-weekly cycles of FOLFOX (85 mg/m2 BSA of oxaliplatin IV + 400 mg/m2 BSA of leucovorin IV + 400 mg/m2 BSA of bolus 5-fluorouracil IV followed by 2400 mg/m2 BSA of continuous 5-fluorouracil IV). It is left to the discretion of the treating medical oncologist which of the two will be administered. In case of (previous) unacceptable toxicity (physician's discretion) to oxaliplatin, FOLFIRI may be prescribed. FOLFIRI (180 mg/m2 BSA of irinotecan IV + 400 mg/m2 BSA of leucovorin IV + 400 mg/m2 BSA of bolus 5-fluorouracil IV followed by 2400 mg/m2 BSA of continuous 5-fluorouracil IV) consists of four two-weekly cycles.
If a patient has stable or responsive disease, induction chemotherapy will be continued with either one three-weekly cycle of CAPOX or two two-weekly cycles of FOLFOX/FOLFIRI.
ChemoradiotherapyRadiation
Concomitant chemotherapy agent: capecitabine
Radiotherapy dose: full course radiotherapy consists of 25x2.0 or 28x1.8 Gy. In case of previous radiotherapy, the radiotherapy dose will consist of 15x2.0 Gy.
Surgery locally recurrent rectal cancerProcedure or surgery
Type of surgery depends on the location of the recurrence and involvement of adjacent structures and is left to the discretion of the operating surgeon.
Intraoperative radiotherapy is optional.
| Study group | Role | What they receive |
|---|---|---|
| Induction chemotherapy + chemoradiotherapy + surgery | Experimental | Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery Receives: Drug: Combination drug; Radiation: Chemoradiotherapy; Procedure: Surgery locally recurrent rectal cancer |
| Neoadjuvant chemotherapy + surgery | Active comparator | Neoadjuvant chemoradiotherapy followed by surgery Receives: Radiation: Chemoradiotherapy; Procedure: Surgery locally recurrent rectal cancer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with a clear resection margin
A resection margin is considered clear (R0), if there are no tumour cells in any of the resection surfaces as determined by microscopy (resection margin > 0mm)
Measured: Scored within 1 one month of surgery
Secondary outcomes (17)
Local recurrence free survival
Measured: Assessed up to 5 years
Progression free survival
Measured: Assessed up to 5 years
Metastasis free survival
Measured: Assessed up to 5 years
Disease free survival
Measured: Assessed up to 5 years
Overall survival
Measured: Assessed up to 5 years
Pathologic response
Scored according to Mandard
Measured: Scored within 1 month of surgery
Toxicity induction chemotherapy
Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Measured: Scored until one month after the last administration of the chemotherapy
Compliance induction chemotherapy
Measured: Scored within 1 month after start chemoradiotherapy
Toxicity chemoradiotherapy
Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Measured: Scored until 3 months after the last administration of the radiotherapy
Compliance chemoradiotherapy
Measured: Evaluation at time of surgery
Number of patients undergoing surgery
Measured: Surgery is scheduled 10-14 weeks after finishing chemoradiotherapy
Surgical characteristics
including data on intra-operative radiotherapy
Measured: Evaluation directly postoperative
Major surgical morbidity
Clavien-Dindo grade 3 or higher
Measured: 30 and 90-days postoperative
Radiological response
mrTRG
Measured: Restaging is performed after 3 cycles of CAPOX (1 cycle is 3 weeks) or 4 cycles of CAPOX/FOLFOX (1 cycle is 2 weeks). Second restaging is performed 4-6 weeks after finishing chemoradiotherapy
Cancer specific quality of life
QLQ-C30
Measured: at baseline, 3 months and 12 months postoperative
Cost-effectiveness
EQ-5D-5L
Measured: at baseline, 3 months and 12 months postoperative
Colorectal cancer specific quality of life
QLQ-CR29
Measured: at baseline, 3 months and 12 months postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2020
- Study start13 Nov 2020
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 364 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Catharina Ziekenhuis Eindhoven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, J. W. A. Burger, Catharina Ziekenhuis Eindhoven
- Investigators
- Pim Burger, MD, Principal investigator, Catharina Ziekenhuis Eindhoven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04389086
- Sponsor's protocol ID
- NL73593
- Acronym
- PelvEx II
- Status last verified
- Sep 2022
- First submitted
- 7 May 2020
- Last updated
- 6 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participant-level datasets and statistical codes will become available upon reasonable request after the results of the study have been published.
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre, Open-label, Randomised, Controlled, Parallel Arms Clinical Trial of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone as Neoadjuvant Treatment for Locally Recurrent Rectal Cancer - PelvEx II
- ClinicalTrials.gov ID
- NCT04389086
- Acronym / sponsor ID
- PelvEx II / NL73593
- Conditions
- Recurrent Rectal Cancer
- Keywords
- Locally recurrent rectal cancer, Neoadjuvant therapy, Induction chemotherapy, Resection margin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 364 participants (estimated)
- Lead sponsor
- Catharina Ziekenhuis EindhovenUniversity, hospital or other
- Study start
- 13 Nov 2020 (actual)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2030 (estimated)
- First posted
- 15 May 2020 (actual)
- 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.
This is a multicentre, open-label, parallel arms, phase IIII study that randomises patients with locally recurrent rectal cancer in a 1:1 ratio to receive either induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Induction chemotherapy + chemoradiotherapy + surgery | Experimental | Drug: Combination drug, Radiation: Chemoradiotherapy, Procedure: Surgery locally recurrent rectal cancerInduction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery |
| Neoadjuvant chemotherapy + surgery | Active comparator | Radiation: Chemoradiotherapy, Procedure: Surgery locally recurrent rectal cancerNeoadjuvant chemoradiotherapy followed by surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18 years or older
- Confirmed locally recurrent rectal cancer after total or partial mesorectal resection for rectal or distal sigmoidal cancer either by histopathology ór clinically proven (evidence on imaging in combination with clinical findings, with consensus in MDT)
- Resectable disease determined by magnetic resonance imaging (MRI) or deemed resectable after neoadjuvant treatment with chemoradiotherapy.
- WHO performance score 0-1
- Written informed consent
Key exclusion criteria (8 listed)
- Radiological evidence of metastatic disease (e.g. liver, lung) at time of randomisation or in the six months prior to randomisation.
- Known homozygous DPD deficiency
- Any chemotherapy in the past 6 months.
- Any contraindication for the planned chemotherapy, as determined by the medical oncologist.
- Radiotherapy in the past 6 months for primary rectal cancer.
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 |
|---|---|---|
| Combination drugAlso: CAPOX, FOLFOX, FOLFIRIInduction chemotherapy consists of either three three-weekly cycles of CAPOX (oxaliplatin 130 mg/m2 BSA IV + capecitabine 1000 mg/m2 BSA, orally, twice daily) or four two-weekly cycles of FOLFOX (85 mg/m2 BSA of oxaliplatin IV + 400 mg/m2 BSA of leucovorin IV + 400 mg/m2 BSA of bolus 5-fluorouracil IV followed by 2400 mg/m2 BSA of continuous 5-fluorouracil IV). It is left to the discretion of the treating medical oncologist which of the two will be administered. In case of (previous) unacceptable toxicity (physician's discretion) to oxaliplatin, FOLFIRI may be prescribed. FOLFIRI (180 mg/m2 BSA of irinotecan IV + 400 mg/m2 BSA of leucovorin IV + 400 mg/m2 BSA of bolus 5-fluorouracil IV followed by 2400 mg/m2 BSA of continuous 5-fluorouracil IV) consists of four two-weekly cycles. If a patient has stable or responsive disease, induction chemotherapy will be continued with either one three-weekly cycle of CAPOX or two two-weekly cycles of FOLFOX/FOLFIRI. | Drug | Induction chemotherapy + chemoradiotherapy + surgery |
| ChemoradiotherapyConcomitant chemotherapy agent: capecitabine Radiotherapy dose: full course radiotherapy consists of 25x2.0 or 28x1.8 Gy. In case of previous radiotherapy, the radiotherapy dose will consist of 15x2.0 Gy. | Radiation | Induction chemotherapy + chemoradiotherapy + surgery, Neoadjuvant chemotherapy + surgery |
| Surgery locally recurrent rectal cancerType of surgery depends on the location of the recurrence and involvement of adjacent structures and is left to the discretion of the operating surgeon. Intraoperative radiotherapy is optional. | Procedure or surgery | Induction chemotherapy + chemoradiotherapy + surgery, Neoadjuvant chemotherapy + surgery |
Primary outcome
Proportion of patients with a clear resection margin
Time frame: Scored within 1 one month of surgery
A resection margin is considered clear (R0), if there are no tumour cells in any of the resection surfaces as determined by microscopy (resection margin > 0mm)
17 secondary outcomes
Local recurrence free survival
Time frame: Assessed up to 5 years
Progression free survival
Time frame: Assessed up to 5 years
Metastasis free survival
Time frame: Assessed up to 5 years
Disease free survival
Time frame: Assessed up to 5 years
Overall survival
Time frame: Assessed up to 5 years
Pathologic response
Time frame: Scored within 1 month of surgery
Toxicity induction chemotherapy
Time frame: Scored until one month after the last administration of the chemotherapy
Compliance induction chemotherapy
Time frame: Scored within 1 month after start chemoradiotherapy
Toxicity chemoradiotherapy
Time frame: Scored until 3 months after the last administration of the radiotherapy
Compliance chemoradiotherapy
Time frame: Evaluation at time of surgery
Number of patients undergoing surgery
Time frame: Surgery is scheduled 10-14 weeks after finishing chemoradiotherapy
Surgical characteristics
Time frame: Evaluation directly postoperative
Major surgical morbidity
Time frame: 30 and 90-days postoperative
Radiological response
Time frame: Restaging is performed after 3 cycles of CAPOX (1 cycle is 3 weeks) or 4 cycles of CAPOX/FOLFOX (1 cycle is 2 weeks). Second restaging is performed 4-6 weeks after finishing chemoradiotherapy
Cancer specific quality of life
Time frame: at baseline, 3 months and 12 months postoperative
Cost-effectiveness
Time frame: at baseline, 3 months and 12 months postoperative
Colorectal cancer specific quality of life
Time frame: at baseline, 3 months and 12 months postoperative
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2022.
- Individual participant dataSharing planned: Yes. Participant-level datasets and statistical codes will become available upon reasonable request after the results of the study have been published.
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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.
Pim Burger, MD principal investigator
Catharina Ziekenhuis Eindhoven
14 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Combination drug, Chemoradiotherapy and Surgery locally recurrent rectal cancer in people with Recurrent Rectal Cancer, run by Catharina Ziekenhuis Eindhoven at 14 sites in 5 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 5 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 6 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Netherlands, Sweden, Belgium, Norway, Portugal. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stefi Nordkamp, MD (0031 40 2398858, stefi.nordkamp@catharinaziekenhuis.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with a clear resection margin (time frame: Scored within 1 one month of surgery). 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 6 Sep 2022.