Induction Chemotherapy for Locally Recurrent Rectal Cancer

NCT ID: NCT04389086

Last Updated: 2022-09-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

364 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-13

Study Completion Date

2030-03-01

Brief Summary

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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)

Detailed Description

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Conditions

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Recurrent Rectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Induction chemotherapy + chemoradiotherapy + surgery

Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery

Group Type EXPERIMENTAL

Combination drug

Intervention Type DRUG

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.

Chemoradiotherapy

Intervention Type RADIATION

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 cancer

Intervention Type PROCEDURE

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.

Neoadjuvant chemotherapy + surgery

Neoadjuvant chemoradiotherapy followed by surgery

Group Type ACTIVE_COMPARATOR

Chemoradiotherapy

Intervention Type RADIATION

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 cancer

Intervention Type PROCEDURE

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.

Interventions

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Combination drug

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 DRUG

Chemoradiotherapy

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 RADIATION

Surgery locally recurrent rectal cancer

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.

Intervention Type PROCEDURE

Other Intervention Names

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CAPOX FOLFOX FOLFIRI

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Catharina Ziekenhuis Eindhoven

OTHER

Sponsor Role lead

Responsible Party

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J. W. A. Burger

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pim Burger, MD

Role: PRINCIPAL_INVESTIGATOR

Catharina Ziekenhuis Eindhoven

Locations

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UZ Gent

Ghent, , Belgium

Site Status NOT_YET_RECRUITING

Amsterdam UMC

Amsterdam, , Netherlands

Site Status RECRUITING

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Site Status RECRUITING

Catharina Hospital

Eindhoven, , Netherlands

Site Status RECRUITING

University Medical Centre Groningen

Groningen, , Netherlands

Site Status RECRUITING

Leids University Medical Centre

Leiden, , Netherlands

Site Status RECRUITING

Haaglanden Medical Centre

Leidschendam, , Netherlands

Site Status RECRUITING

Maastricht University Medical Centre

Maastricht, , Netherlands

Site Status RECRUITING

Erasmus Medical Centre

Rotterdam, , Netherlands

Site Status RECRUITING

Oslo Universitetssykehus

Oslo, , Norway

Site Status NOT_YET_RECRUITING

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.

Lisbon, , Portugal

Site Status NOT_YET_RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Site Status NOT_YET_RECRUITING

Skåne Universitetssjukhuset

Malmo, , Sweden

Site Status NOT_YET_RECRUITING

Karolinska Universitetssjukhuset

Stockholm, , Sweden

Site Status NOT_YET_RECRUITING

Countries

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Belgium Netherlands Norway Portugal Sweden

Central Contacts

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Stefi Nordkamp, MD

Role: CONTACT

0031 40 2398858

Floor Piqeur, MD

Role: CONTACT

0031 40 2397152

Facility Contacts

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Gabrielle van Ramshorst, MD, PhD

Role: primary

Miranda Kusters, MD, PhD

Role: primary

Arend Aalbers, MD, PhD

Role: primary

Stefi Nordkamp, MD

Role: primary

0031 40 2398858

Pim Burger, MD, PhD

Role: backup

Klaas Havenga, MD, PhD

Role: primary

Fabian Holman, Md, PhD

Role: primary

Andreas Marinelli, MD, PhD

Role: primary

Jarno Melenhorst, MD, PhD

Role: primary

Cornelis Verhoef, MD, PhD

Role: primary

Marianne Guren, MD, PhD

Role: primary

João Maciel, MD, PhD

Role: primary

Eva Angenete, MD, PhD

Role: primary

Sofia Heyman, MD, PhD

Role: backup

Pamela Buchwald, MD, PhD

Role: primary

Henrik Iversen, MD, PhD

Role: primary

Other Identifiers

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NL73593

Identifier Type: -

Identifier Source: org_study_id

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