Induction Chemotherapy for Locally Recurrent Rectal Cancer

NCT04389086 | Recruiting Phase 3 DMC

• 1 other identifier: NL73593
• Study Type: interventional
• Target: 364
• Locations: 5 countries
• Sites: 14

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)

Conditions

Recurrent Rectal Cancer

Keywords

Locally recurrent rectal cancer; Neoadjuvant therapy; Induction chemotherapy; Resection margin

Outcome Measures

Primary Outcomes (1)

• 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)

  Scored within 1 one month of surgery

Secondary Outcomes (17)

• Local recurrence free survival

  Assessed up to 5 years

• Progression free survival

  Assessed up to 5 years

• Metastasis free survival

  Assessed up to 5 years

• Disease free survival

  Assessed up to 5 years

• Overall survival

  Assessed up to 5 years

Study Arms (2)

Induction chemotherapy + chemoradiotherapy + surgery

EXPERIMENTAL

Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery

Drug: Combination drug; Radiation: Chemoradiotherapy; Procedure: Surgery locally recurrent rectal cancer

Neoadjuvant chemotherapy + surgery

ACTIVE COMPARATOR

Neoadjuvant chemoradiotherapy followed by surgery

Radiation: Chemoradiotherapy; Procedure: Surgery locally recurrent rectal cancer

Interventions

Combination drug 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.

Also known as: CAPOX, FOLFOX, FOLFIRI

Induction chemotherapy + chemoradiotherapy + surgery

Chemoradiotherapy 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.

Induction chemotherapy + chemoradiotherapy + surgery; Neoadjuvant chemotherapy + surgery

Surgery locally recurrent rectal cancer 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.

Induction chemotherapy + chemoradiotherapy + surgery; Neoadjuvant chemotherapy + surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Catharina Ziekenhuis Eindhoven: lead

Study Sites (14)

UZ Gent

Ghent, Belgium

NOT YET RECRUITING

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

Antoni van Leeuwenhoek

Amsterdam, Netherlands

RECRUITING

Catharina Hospital

Eindhoven, 5623EJ, Netherlands

RECRUITING

University Medical Centre Groningen

Groningen, Netherlands

RECRUITING

Leids University Medical Centre

Leiden, Netherlands

RECRUITING

Haaglanden Medical Centre

Leidschendam, Netherlands

RECRUITING

Maastricht University Medical Centre

Maastricht, Netherlands

RECRUITING

Erasmus Medical Centre

Rotterdam, Netherlands

RECRUITING

Oslo Universitetssykehus

Oslo, Norway

NOT YET RECRUITING

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

Lisbon, Portugal

NOT YET RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, Sweden

NOT YET RECRUITING

Skåne Universitetssjukhuset

Malmo, Sweden

NOT YET RECRUITING

Karolinska Universitetssjukhuset

Stockholm, Sweden

NOT YET RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms; Margins of Excision

Interventions

Drug Combinations; Folfox protocol; IFL protocol; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Pim Burger, MD

  Catharina Ziekenhuis Eindhoven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefi Nordkamp, MD

CONTACT

0031 40 2398858; stefi.nordkamp@catharinaziekenhuis.nl

Floor Piqeur, MD

CONTACT

0031 40 2397152; floor.piqeur@catharinaziekenhuis.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 15, 2020
• Study Start: November 13, 2020
• Primary Completion: March 1, 2024
• Study Completion (Estimated): March 1, 2030
• Last Updated: September 6, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The full protocol and Dutch informed consent forms are publicly accessible after approval of the medical ethics committee.

Locations

SE (3); BE (1); NL (8); NO (1); PT (1)