Multicentre, open-label, randomized, controlled, parallel arms clinical trial of induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer (PelvEx II)

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

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Trial duration

28 Oct 2020 → ongoing

Decision date (initial)

2024-04-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512526-28-00

EudraCT number

2020-002141-42

ClinicalTrials.gov

NCT04389086

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the rate of resections with clear resection margins between both arms.

Secondary objectives 17

1. To compare the local re-recurrence free survival between both arms.
2. To compare the progression free survival between both arms.
3. To compare the metastasis free survival between both arms.
4. To compare the disease free survival between both arms.
5. To compare the overall survival between both arms.
6. To determine the pathologic response and compare this between both arms.
7. To assess the objective radiological response to the neoadjuvant treatment.
8. To determine the toxicity related to the administration of induction chemotherapy in the experimental arm.
9. To determine the compliance to induction chemotherapy in the experimental arm.
10. To compare the toxicity related to the administration of chemoradiotherapy between both arms.
11. To compare the compliance to chemoradiotherapy between both arms.
12. To compare the number of patients undergoing surgery between both arms.
13. To compare surgical characteristics between both arms.
14. To compare the rate of major surgical complications between both arms.
15. To compare the quality of life between both arms.
16. To determine the cost-effectiveness and –utility.
17. To systematically collect blood and tissue samples from enrolled patients for future translational research.

Conditions and MedDRA coding

Locally recurrent rectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 18 years or older
2. Confirmed locally recurrent rectal cancer after total or partial mesorectal resection for rectal cancer or distal sigmoidal cancer, either by; histopathology ór; clinically proven (evidence on imaging in combination with clinical findings, with consensus in MDT)
3. Resectable disease determined by magnetic resonance imaging (MRI) or deemed resectable after neoadjuvant treatment with chemoradiotherapy. Expected gross incomplete resection with overt tumour remaining in the patient after resection, encasement of the ischiadic nerve and invasion of the cortex and/or neuroforamina from S2 and upwards are considered not resectable.
4. WHO performance score 0-1
5. Written informed consent

Exclusion criteria 8

1. Radiological evidence of metastatic disease (e.g. liver, lung) at time of randomisation or in the six months prior to randomisation. Patients with enlarged iliac lymph nodes, enlarged inguinal lymph nodes and aspecific lung noduli are not excluded from inclusion.
2. Homozygous DPD deficiency (if known in advance)
3. Any chemotherapy in the past 6 months.
4. Radiotherapy in the past 6 months for primary rectal cancer.
5. Any contraindication for the planned chemotherapy (e.g. severe allergy, pregnancy, kidney dysfunction, thrombocytopenia), as determined by the medical oncologist.
6. 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.
7. Any contraindication for surgery, as determined by the surgeon and/or anaesthesiologist.
8. Concurrent malignancies that interfere with the planned study treatment or the prognosis of resected LRRC.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The rate of clear resection margins after surgery

Secondary endpoints 13

1. Local re-recurrence free survival
2. Progression free survival
3. Distant metastasis free survival
4. Disease free survival
5. Overall survival
6. Pathologic response
7. Radiological response
8. Systemic therapy related toxicity (NCI-CTCAE v5.0 grade ≥3)
9. The number of patients completing neoadjuvant treatment
10. Surgical characteristics
11. Major postoperative complications (Clavien-Dindo ≥3) up to 90-days postoperatively
12. Quality of life
13. Cost-effectiveness

Investigational products

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

Test 6

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

Davy Creemers

Public contact point

Organisation

Catharina Ziekenhuis Stichting

Contact name

Davy Creemers

Third parties 3

Locations

5 EU/EEA countries · 33 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 25 files

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

Application history

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