Back to resultsInduction Chemotherapy for Locally Recurrent Rectal Cancer (PelvEx II)
Primary Purpose
Recurrent Rectal Cancer
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Combination drug
Chemoradiotherapy
Surgery locally recurrent rectal cancer
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Rectal Cancer focused on measuring Locally recurrent rectal cancer, Neoadjuvant therapy, Induction chemotherapy, Resection margin
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- UZ Gent
- Amsterdam UMCRecruiting
- Antoni van LeeuwenhoekRecruiting
- Catharina HospitalRecruiting
- University Medical Centre GroningenRecruiting
- Leids University Medical CentreRecruiting
- Haaglanden Medical CentreRecruiting
- Maastricht University Medical CentreRecruiting
- Erasmus Medical CentreRecruiting
- Oslo Universitetssykehus
- Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.
- Sahlgrenska Universitetssjukhuset
- Skåne Universitetssjukhuset
- Karolinska Universitetssjukhuset
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Induction chemotherapy + chemoradiotherapy + surgery
Neoadjuvant chemotherapy + surgery
Arm Description
Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery
Neoadjuvant chemoradiotherapy followed by surgery
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Local recurrence free survival
Progression free survival
Metastasis free survival
Disease free survival
Overall survival
Pathologic response
Scored according to Mandard
Toxicity induction chemotherapy
Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Compliance induction chemotherapy
Toxicity chemoradiotherapy
Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Compliance chemoradiotherapy
Number of patients undergoing surgery
Surgical characteristics
including data on intra-operative radiotherapy
Major surgical morbidity
Clavien-Dindo grade 3 or higher
Radiological response
mrTRG
Cancer specific quality of life
QLQ-C30
Cost-effectiveness
EQ-5D-5L
Colorectal cancer specific quality of life
QLQ-CR29
Full Information
NCT ID
NCT04389086
First Posted
May 7, 2020
Last Updated
September 1, 2022
Sponsor
Catharina Ziekenhuis Eindhoven
1. Study Identification
Unique Protocol Identification Number
NCT04389086
Brief Title
Induction Chemotherapy for Locally Recurrent Rectal Cancer
Acronym
PelvEx II
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 13, 2020 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Catharina Ziekenhuis Eindhoven
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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 arm)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Rectal Cancer
Keywords
Locally recurrent rectal cancer, Neoadjuvant therapy, Induction chemotherapy, Resection margin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
364 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Induction chemotherapy + chemoradiotherapy + surgery
Arm Type
Experimental
Arm Description
Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery
Arm Title
Neoadjuvant chemotherapy + surgery
Arm Type
Active Comparator
Arm Description
Neoadjuvant chemoradiotherapy followed by surgery
Intervention Type
Drug
Intervention Name(s)
Combination drug
Other Intervention Name(s)
CAPOX, FOLFOX, FOLFIRI
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Chemoradiotherapy
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Surgery locally recurrent rectal cancer
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of patients with a clear resection margin
Description
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)
Time Frame
Scored within 1 one month of surgery
Secondary Outcome Measure Information:
Title
Local recurrence free survival
Time Frame
Assessed up to 5 years
Title
Progression free survival
Time Frame
Assessed up to 5 years
Title
Metastasis free survival
Time Frame
Assessed up to 5 years
Title
Disease free survival
Time Frame
Assessed up to 5 years
Title
Overall survival
Time Frame
Assessed up to 5 years
Title
Pathologic response
Description
Scored according to Mandard
Time Frame
Scored within 1 month of surgery
Title
Toxicity induction chemotherapy
Description
Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Time Frame
Scored until one month after the last administration of the chemotherapy
Title
Compliance induction chemotherapy
Time Frame
Scored within 1 month after start chemoradiotherapy
Title
Toxicity chemoradiotherapy
Description
Adverse events grade 3 or higher according to the NCI-CTCAE v5.0
Time Frame
Scored until 3 months after the last administration of the radiotherapy
Title
Compliance chemoradiotherapy
Time Frame
Evaluation at time of surgery
Title
Number of patients undergoing surgery
Time Frame
Surgery is scheduled 10-14 weeks after finishing chemoradiotherapy
Title
Surgical characteristics
Description
including data on intra-operative radiotherapy
Time Frame
Evaluation directly postoperative
Title
Major surgical morbidity
Description
Clavien-Dindo grade 3 or higher
Time Frame
30 and 90-days postoperative
Title
Radiological response
Description
mrTRG
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
Title
Cancer specific quality of life
Description
QLQ-C30
Time Frame
at baseline, 3 months and 12 months postoperative
Title
Cost-effectiveness
Description
EQ-5D-5L
Time Frame
at baseline, 3 months and 12 months postoperative
Title
Colorectal cancer specific quality of life
Description
QLQ-CR29
Time Frame
at baseline, 3 months and 12 months postoperative
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stefi Nordkamp, MD
Phone
0031 40 2398858
Email
stefi.nordkamp@catharinaziekenhuis.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Floor Piqeur, MD
Phone
0031 40 2397152
Email
floor.piqeur@catharinaziekenhuis.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pim Burger, MD
Organizational Affiliation
Catharina Ziekenhuis Eindhoven
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Gent
City
Gent
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabrielle van Ramshorst, MD, PhD
Facility Name
Amsterdam UMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miranda Kusters, MD, PhD
Facility Name
Antoni van Leeuwenhoek
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arend Aalbers, MD, PhD
Facility Name
Catharina Hospital
City
Eindhoven
ZIP/Postal Code
5623EJ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefi Nordkamp, MD
Phone
0031 40 2398858
Email
pelvex2@catharinaziekenhuis.nl
First Name & Middle Initial & Last Name & Degree
Pim Burger, MD, PhD
Email
pim.burger@catharinaziekenhuis.nl
Facility Name
University Medical Centre Groningen
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Klaas Havenga, MD, PhD
Facility Name
Leids University Medical Centre
City
Leiden
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabian Holman, Md, PhD
Facility Name
Haaglanden Medical Centre
City
Leidschendam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Marinelli, MD, PhD
Facility Name
Maastricht University Medical Centre
City
Maastricht
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jarno Melenhorst, MD, PhD
Facility Name
Erasmus Medical Centre
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cornelis Verhoef, MD, PhD
Facility Name
Oslo Universitetssykehus
City
Oslo
Country
Norway
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marianne Guren, MD, PhD
Facility Name
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.
City
Lisbon
Country
Portugal
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
João Maciel, MD, PhD
Facility Name
Sahlgrenska Universitetssjukhuset
City
Göteborg
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Angenete, MD, PhD
First Name & Middle Initial & Last Name & Degree
Sofia Heyman, MD, PhD
Facility Name
Skåne Universitetssjukhuset
City
Malmö
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pamela Buchwald, MD, PhD
Facility Name
Karolinska Universitetssjukhuset
City
Stockholm
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henrik Iversen, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Participant-level datasets and statistical codes will become available upon reasonable request after the results of the study have been published.
IPD Sharing Time Frame
The full protocol and Dutch informed consent forms are publicly accessible after approval of the medical ethics committee.
Learn more about this trial
Induction Chemotherapy for Locally Recurrent Rectal Cancer
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