Induction chemotherapy for locally advanced rectal cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Catharina Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Neoplasms [C04], Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04]

Trial duration

21 Jul 2021 → ongoing

Decision date (initial)

2024-03-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMw

External identifiers

EU CT number

2023-509758-74-00

EudraCT number

2020-003134-20

ClinicalTrials.gov

NCT04838496

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective of this study is to evaluate if the addition of induction chemotherapy with FOLFOXIRI leads to a higher pathological complete response (pCR) rate and clinical complete response (cCR) rate at 1 year in patients with hr-LARC compared to the currently available literature regarding hr-LARC patients treated with (chemo)radiotherapy alone or followed by consolidation chemotherapy.

Secondary objectives 18

1. To determine the recurrence free survival
2. To determine the distant metastasis free survival
3. To determine the progression-free survival
4. To determine the disease-free survival
5. To determine the overall survival
6. To determine the radiological response after induction chemotherapy
7. To determine the radiological response after induction chemotherapy and chemoradiotherapy
8. To determine the pathological response as determined by Mandard grading system
9. To determine the toxicity related to the administration of induction chemotherapy
10. To determine the compliance related to the administration of induction chemotherapy
11. To determine the toxicity related to the administration of chemoradiotherapy
12. To determine the compliance related to the administration of chemoradiotherapy
13. To determine the number of patients undergoing surgery
14. To determine the type and extent of surgery after neoadjuvant therapy
15. To determine the major surgical complications rate
16. To determine the quality of life
17. To determine the cost-effectiveness and -utility
18. To systemically collect blood and tissue samples for future translational research

Conditions and MedDRA coding

Locally advanced rectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 18 years or older
2. WHO performance score 0-1
3. Fit for (modified dose) triple chemotherapy (FOLFOXIRI)
4. Histopathologically confirmed rectal cancer
5. Lower border of the tumour located on or below the sigmoidal take-off as established on MRI of the pelvis
6. Confirmed high-risk locally advanced rectal cancer, at high risk of treatment failure, meeting one of the following imaging based criteria: *Tumour invasion of the mesorectal fascia (MRF+); *The presence of grade 4 extramural venous invasion (mrEMVI); *The presence of tumour deposits (TD); *The presence of bilateral extramesorectal lymph nodes with a short-axis size ≥ 7mm (LLN) or extensive LLN involving pelvic side wall structures, at high risk of an incomplete resection
7. Resectable disease as determined on magnetic resonance imaging (MRI) or deemed resectable disease after neo-adjuvant treatment (Expected gross incomplete resection with overt tumour remaining in the patient after resection, tumour invasion in the neuroforamina, encasement of the sciatic nerve and invasion of the cortex from S2 and upwards are considered not resectable)
8. Written informed consent

Exclusion criteria 8

1. Evidence of metastatic disease at time of inclusion or within six months prior to inclusion except for patients with enlarged iliac or inguinal lymph nodes and aspecific lung nodules
2. Homozygous DPD deficiency
3. Any chemotherapy within the past 6 months
4. Any contraindication for the planned systemic therapy (e.g. severe allergy, pregnancy, kidney dysfunction and thrombocytopenia), as determined by the medical oncologist
5. Previous radiotherapy in the pelvic area precluding chemoradiotherapy with a dose of 50-50.4 Gy
6. Any contraindication for the planned chemoradiotherapy (e.g. severe allergy to the chemotherapy agent or no possibility to receive radiotherapy), as determined by the medical oncologist and/or radiation oncologist
7. Any contraindication to undergo surgery, as determined by the surgeon and/or anaesthesiologist
8. Concurrent malignancies that interfere with the planned study treatment or the prognosis of the resected tumour

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate if the addition of induction chemotherapy with FOLFOXIRI leads to a higher pathological complete response (pCR) rate and clinical complete response (cCR) rate at 1 year in patients with high-risk locally advanced rectal cancer compared to the currently available literature regarding high-risk locally advanced rectal cancer patients treated with (chemo)radiotherapy alone or followed by consolidation chemotherapy

Secondary endpoints 18

1. To determine the recurrence free survival
2. To determine the distant metastasis free survival
3. To determine the progression-free survival
4. To determine the disease-free survival
5. To determine the overall survival
6. To determine the radiological response after induction chemotherapy
7. To determine the radiological response after induction chemotherapy and chemoradiotherapy
8. To determine the pathological response as determined by Mandard grading system
9. To determine the toxicity related to the administration of induction chemotherapy
10. To determine the compliance related to the administration of induction chemotherapy
11. To determine the toxicity related to the administration of chemoradiotherapy
12. To determine the compliance related to the administration of chemoradiotherapy
13. To determine the number of patients undergoing surgery
14. To determine the type and extent of surgery after neoadjuvant therapy
15. To determine the major surgical complications rate
16. To determine the quality of life
17. To determine the cost-effectiveness and -utility
18. To systematically collect blood and tissue samples for future translational research

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Catharina Ziekenhuis Stichting

Sponsor organisation

Catharina Ziekenhuis Stichting

Address

Michelangelolaan 2

City

Eindhoven

Postcode

5623 EJ

Country

Netherlands

Scientific contact point

Organisation

Catharina Ziekenhuis Stichting

Contact name

Wetenschapsbureau

Public contact point

Organisation

Catharina Ziekenhuis Stichting

Contact name

Wetenschapsbureau

Third parties 2

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 1 file

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications