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Induction Chemotherapy for Locally Recurrent Rectal Cancer (PelvEx II)

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ClinicalTrials.gov Identifier: NCT04389086
Recruitment Status : Recruiting
First Posted : May 15, 2020
Last Update Posted : May 10, 2021
Sponsor:
Information provided by (Responsible Party):
J. W. A. Burger, Catharina Ziekenhuis Eindhoven

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)

Condition or disease Intervention/treatment Phase
Recurrent Rectal Cancer Drug: Combination drug Radiation: Chemoradiotherapy Procedure: Surgery locally recurrent rectal cancer Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 364 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 13, 2020
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : March 1, 2030

Arm Intervention/treatment
Experimental: Induction chemotherapy + chemoradiotherapy + surgery
Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery
Drug: 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.

Other Names:
  • CAPOX
  • FOLFOX
  • FOLFIRI

Radiation: 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.


Procedure: 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.


Active Comparator: Neoadjuvant chemotherapy + surgery
Neoadjuvant chemoradiotherapy followed by surgery
Radiation: 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.


Procedure: 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.





Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Local recurrence free survival [ Time Frame: Assessed up to 5 years ]
  2. Progression free survival [ Time Frame: Assessed up to 5 years ]
  3. Metastasis free survival [ Time Frame: Assessed up to 5 years ]
  4. Disease free survival [ Time Frame: Assessed up to 5 years ]
  5. Overall survival [ Time Frame: Assessed up to 5 years ]
  6. Pathologic response [ Time Frame: Scored within 1 month of surgery ]
    Scored according to Mandard

  7. Toxicity induction chemotherapy [ Time Frame: Scored until one month after the last administration of the chemotherapy ]
    Adverse events grade 3 or higher according to the NCI-CTCAE v5.0

  8. Compliance induction chemotherapy [ Time Frame: Scored within 1 month after start chemoradiotherapy ]
  9. Toxicity chemoradiotherapy [ Time Frame: Scored until 3 months after the last administration of the radiotherapy ]
    Adverse events grade 3 or higher according to the NCI-CTCAE v5.0

  10. Compliance chemoradiotherapy [ Time Frame: Evaluation at time of surgery ]
  11. Number of patients undergoing surgery [ Time Frame: Surgery is scheduled 10-14 weeks after finishing chemoradiotherapy ]
  12. Surgical characteristics [ Time Frame: Evaluation directly postoperative ]
    including data on intra-operative radiotherapy

  13. Major surgical morbidity [ Time Frame: 30 and 90-days postoperative ]
    Clavien-Dindo grade 3 or higher

  14. 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 ]
    mrTRG

  15. Cancer specific quality of life [ Time Frame: at baseline, 3 months and 12 months postoperative ]
    QLQ-C30

  16. Cost-effectiveness [ Time Frame: at baseline, 3 months and 12 months postoperative ]
    EQ-5D-5L

  17. Colorectal cancer specific quality of life [ Time Frame: at baseline, 3 months and 12 months postoperative ]
    QLQ-CR29



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years or older
  • Confirmed locally recurrent rectal cancer after total or partial mesorectal resection for rectal 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.
  • Homozygous DPD deficiency
  • Any chemotherapy in the past 6 months.
  • Any contraindication for the planned chemotherapy (e.g. severe allergy, pregnancy, kidney dysfunction with creatinine clearance of <30ml/min, thrombocytopenia of <100x109/L), as determined by the medical oncologist.
  • Radiotherapy in the past 6 months for primary rectal cancer.
  • Any contraindication for the planned chemoradiotherapy (e.g. severe allergy to chemotherapy agent, no possibility for radiotherapy due to previous radiotherapy), 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04389086


Contacts
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Contact: Stefi Nordkamp, MD 0031 40 2398858 stefi.nordkamp@catharinaziekenhuis.nl
Contact: Eva Voogt, MD 0031 40 2397152 eva.voogt@catharinaziekenhuis.nl

Locations
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Belgium
UZ Gent Not yet recruiting
Gent, Belgium
Contact: Gabrielle van Ramshorst         
Netherlands
Amsterdam UMC Not yet recruiting
Amsterdam, Netherlands, 1081 HV
Contact: Miranda Kusters, MD, PhD         
Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands
Contact: Arend Aalbers, MD         
Catharina Hospital Recruiting
Eindhoven, Netherlands, 5623EJ
Contact: Stefi Nordkamp, MD    0031 40 2398858    pelvex2@catharinaziekenhuis.nl   
Contact: Pim Burger, MD, PhD       pim.burger@catharinaziekenhuis.nl   
University Medical Centre Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Klaas Havenga, MD, PhD         
Leids University Medical Centre Recruiting
Leiden, Netherlands
Contact: Fabian Holman         
Haaglanden Medical Centre Recruiting
Leidschendam, Netherlands, 2262 BA
Contact: Andreas Marinelli, MD, PhD         
Maastricht University Medical Centre Not yet recruiting
Maastricht, Netherlands, 6229 HX
Contact: Jarno Melenhorst, MD, PhD         
Erasmus Medical Centre Recruiting
Rotterdam, Netherlands, 3015 GD
Contact: Cornelis Verhoef, MD, PhD         
Sponsors and Collaborators
Catharina Ziekenhuis Eindhoven
Investigators
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Principal Investigator: Pim Burger, MD Catharina Ziekenhuis Eindhoven
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Responsible Party: J. W. A. Burger, MD, PhD, Catharina Ziekenhuis Eindhoven
ClinicalTrials.gov Identifier: NCT04389086    
Other Study ID Numbers: NL73593
First Posted: May 15, 2020    Key Record Dates
Last Update Posted: May 10, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Participant-level datasets and statistical codes will become available upon reasonable request after the results of the study have been published.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: The full protocol and Dutch informed consent forms will be publicly accessible after approval of the medical ethics committee.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by J. W. A. Burger, Catharina Ziekenhuis Eindhoven:
Locally recurrent rectal cancer
Neoadjuvant therapy
Induction chemotherapy
Resection margin
Additional relevant MeSH terms:
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Rectal Neoplasms
Recurrence
Disease Attributes
Pathologic Processes
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases