Induction Chemotherapy for Locally Recurrent Rectal Cancer

Recurrent Rectal Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04389086
• Other study ID #: NL73593
• Status: Recruiting
• Phase: Phase 3
• Start date: November 13, 2020
• Est. completion date: March 1, 2030

Study information

• Verified date: September 2022
• Source: Catharina Ziekenhuis Eindhoven
• Contact: Stefi Nordkamp, MD
• Phone: 0031 40 2398858
• Email: stefi.nordkamp[@]catharinaziekenhuis.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 364
• Est. completion date: March 1, 2030
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Neoplasms
• Recurrence
• Recurrent Rectal Cancer

Intervention

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.

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.

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	Antoni van Leeuwenhoek	Amsterdam
Netherlands	Catharina Hospital	Eindhoven
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	Leids University Medical Centre	Leiden
Netherlands	Haaglanden Medical Centre	Leidschendam
Netherlands	Maastricht University Medical Centre	Maastricht
Netherlands	Erasmus Medical Centre	Rotterdam
Norway	Oslo Universitetssykehus	Oslo
Portugal	Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.	Lisbon
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Skåne Universitetssjukhuset	Malmö
Sweden	Karolinska Universitetssjukhuset	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Catharina Ziekenhuis Eindhoven

Countries where clinical trial is conducted

Belgium,  Netherlands,  Norway,  Portugal,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Local recurrence free survival		Assessed up to 5 years
Secondary	Progression free survival		Assessed up to 5 years
Secondary	Metastasis free survival		Assessed up to 5 years
Secondary	Disease free survival		Assessed up to 5 years
Secondary	Overall survival		Assessed up to 5 years
Secondary	Pathologic response	Scored according to Mandard	Scored within 1 month of surgery
Secondary	Toxicity induction chemotherapy	Adverse events grade 3 or higher according to the NCI-CTCAE v5.0	Scored until one month after the last administration of the chemotherapy
Secondary	Compliance induction chemotherapy		Scored within 1 month after start chemoradiotherapy
Secondary	Toxicity chemoradiotherapy	Adverse events grade 3 or higher according to the NCI-CTCAE v5.0	Scored until 3 months after the last administration of the radiotherapy
Secondary	Compliance chemoradiotherapy		Evaluation at time of surgery
Secondary	Number of patients undergoing surgery		Surgery is scheduled 10-14 weeks after finishing chemoradiotherapy
Secondary	Surgical characteristics	including data on intra-operative radiotherapy	Evaluation directly postoperative
Secondary	Major surgical morbidity	Clavien-Dindo grade 3 or higher	30 and 90-days postoperative
Secondary	Radiological response	mrTRG	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
Secondary	Cancer specific quality of life	QLQ-C30	at baseline, 3 months and 12 months postoperative
Secondary	Cost-effectiveness	EQ-5D-5L	at baseline, 3 months and 12 months postoperative
Secondary	Colorectal cancer specific quality of life	QLQ-CR29	at baseline, 3 months and 12 months postoperative