Clinical trial NCT04389086: Induction Chemotherapy for Locally Recurrent Rectal Cancer
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Recurrent Rectal Cancer
Keywords: Locally recurrent rectal cancer
Neoadjuvant therapy
Induction chemotherapy
Resection margin
Lead sponsor: Catharina Ziekenhuis Eindhoven
Sponsor class: OTHER
First posted: 2020-05-15
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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.

Primary outcomes:
measure: Proportion of patients with a clear resection margin
timeFrame: Scored within 1 one month of surgery
Secondary outcomes:
measure: Local recurrence free survival
timeFrame: Assessed up to 5 years
measure: Progression free survival
timeFrame: Assessed up to 5 years
measure: Metastasis free survival
timeFrame: Assessed up to 5 years
measure: Disease free survival
timeFrame: Assessed up to 5 years
measure: Overall survival
timeFrame: Assessed up to 5 years
measure: Pathologic response
timeFrame: Scored within 1 month of surgery
measure: Toxicity induction chemotherapy
timeFrame: Scored until one month after the last administration of the chemotherapy
measure: Compliance induction chemotherapy
timeFrame: Scored within 1 month after start chemoradiotherapy
measure: Toxicity chemoradiotherapy
timeFrame: Scored until 3 months after the last administration of the radiotherapy
measure: Compliance chemoradiotherapy
timeFrame: Evaluation at time of surgery
measure: Number of patients undergoing surgery
timeFrame: Surgery is scheduled 10-14 weeks after finishing chemoradiotherapy
measure: Surgical characteristics
timeFrame: Evaluation directly postoperative
measure: Major surgical morbidity
timeFrame: 30 and 90-days postoperative
measure: Radiological response
timeFrame: 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
measure: Cancer specific quality of life
timeFrame: at baseline, 3 months and 12 months postoperative
measure: Cost-effectiveness
timeFrame: at baseline, 3 months and 12 months postoperative
measure: Colorectal cancer specific quality of life
timeFrame: at baseline, 3 months and 12 months postoperative
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: UZ Gent
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
city: Leiden
country: Netherlands
facility: Leids University Medical Centre
city: Leidschendam
country: Netherlands
facility: Haaglanden Medical Centre
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Oslo
country: Norway
facility: Oslo Universitetssykehus
city: Lisbon
country: Portugal
facility: Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Malmö
country: Sweden
facility: Skåne Universitetssjukhuset
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
Study officials:
affiliation: Catharina Ziekenhuis Eindhoven
name: Pim Burger, MD
role: PRINCIPAL_INVESTIGATOR
References: