PRODIGE 87 FOXTROT II : Personalising and refining neo-adjuvant chemotherapy in locally advanced but resectable colon cancer in the elderly of 70 years old or more

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Dijon

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

7 Jun 2024 → ongoing

Decision date (initial)

2023-08-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PHRC 2022

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective is to demonstrate that the proportion of patients alive and disease-free at 3 years after randomization treated with 6 weeks (3 courses) of NeoAdjuvant Chemotherapy (FOLFOX) followed by surgery is superior compared to those going Straight To Surgery.

Secondary objectives 11

1. Tumour regression grade on the surgical sample at the time of surgery
2. Tumour regression score on the surgical sample at the time of surgery
3. Histopathological endpoints on the surgical sample at the time of surgery
4. Short-term efficacy and association with longer-term outcomes (recurrence within 1 year after surgery and downstaging post-NAC )
5. Safety and toxicity
6. Cancer specific survival
7. Overall survival
8. Surgical morbidity and mortality
9. Patient-reported outcomes
10. Geriatric assessment scoring
11. Medium and long-terms efficacy

Conditions and MedDRA coding

colon carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Biopsy-confirmed adenocarcinoma of the colon, high-grade dysplasia is acceptable with unequivocal radiological evidence of invasive cancer
2. Radiological stage T3/T4 and N0/N1/N2 and M0
3. Patient eligible for curative surgery
4. No clinical or radiological evidence of bowel obstruction
5. Age ≥ 70 at the time of registration
6. pMMR/MSS tumour status
7. Colon cancer specialist assessed fit to receive 6 weeks (3 courses) of NAC with FOLFOX and surgery
8. Homozygous for DPYD germline mutation
9. Homozygous for DPYD germline mutation
10. Adequate renal biochemistry
11. Adequate hepatobiliary function
12. Patient able to understand and willing to provide written informed consent for the study
13. Patient affiliated to a social security scheme

Exclusion criteria 19

1. Any patient for whom radiotherapy is advised by the multidisciplinary team metting
2. Strong evidence of distant metastases or peritoneal nodules
3. Peritonitis
4. T1-T2
5. Serious medical comorbidity, as assessed by leading clinician
6. Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <10%
7. Known dMMR/ MSI-H tumour status
8. Have a peripheral sensitive neuropathy with functional impairment
9. Recent (within four weeks prior to randomisation) or concomitant treatment with brivudine, sorivudine or their chemically related analogues
10. Person under guardianship, curatorship, and safeguard of justice or person deprived of liberty
11. Impossible to undergo the medical follow-up of the trial for geographical, social or psychological reasons
12. Hypersensitivity to the active substance of the trial treatments or to any of the excipients
13. Patient with poor nutritional status at appreciation by each clinician
14. bone marrow hypoplasia
15. Potentially severe infection 1 month before NAC
16. Patients who have received live attenuated vaccines (yellow fever, varicella, shingles, measles, mumps, rubella, tuberculosis, rotavirus, influenza) 1 month before NAC
17. Any chronic condition not balanced in the last 6 months: liver failure, renal failure, respiratory failure, heart failu
18. QT/QTc interval > 450 msec for men and > 470 msec for women
19. Known Pernicious anaemia or other anaemias due to vitamin B12 deficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival (DFS), is defined as the time from randomization to the first event (i.e, either a first recurrence local or metastatic), treatment failure, or death from any cause.

Secondary endpoints 9

1. Histopathological evaluation: histopathologic description will be made by evaluating the following criteria: FIT, SIR, tumor cell density, maximum tumor size, depth of invasion, apical node involvement, peritoneal involvement, lymph node involvement, R1/R2 resection rate
2. Short-term efficacy assessment of disease stage reduction following neoadjuvant chemotherapy within one year after surgery.
3. Safety and toxicity: Will be assessed by treatment-related toxicities according to NCI-CTCAE version 5.0.
4. Overall and cancer-specific survival: defined as the time from the date of randomisation to the date of death from any cause for overall survival, and related to the cancer disease for cancer-specific survival. Patients alive will be censored at their last news.
5. Rate of surgical morbidity defined as the percentage of grade I/II/IV/V complications according to the Clavien-Dindo classification, will be assessed early, between 4 and 12 weeks after surgery, and late, up to one year after surgery
6. Post-operative mortality defined as any death within 90 days after surgery or within the hospital stay
7. The presence and absence of adjuvant chemotherapy will be described
8. Quality of life will be assessed using the cancer-specific QLQ-C30 and colon cancer-specific QLQ-CR29 questionnaires and the EQ-5D-5L questionnaire. Elderly EORTC module QLQ-QLD14 will also be used
9. Geriatric assessment will be performed by the following questionnaires: G8, IADL, ADL, functional domain and G-code. The health of the elderly will be explored and assessed through these tools, at baseline, in the 12 weeks following surgery, at 1 year after surgery and 3 years after surgery

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Dijon

Sponsor organisation

Centre Hospitalier Universitaire De Dijon

Address

1 Boulevard Jeanne D Arc, Bp 77908 Bp 77908

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

coordinator

Public contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

coordinator

Third parties 1

Locations

2 EU/EEA countries · 70 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 11 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