Safety and Efficacy of Neoadjuvant immunotherapy with Durvalumab (MEDI 4736) in combination with neoadjuvant chemotherapy (Gemcitabin/Cisplatin or Gemcitabin/Carboplatin) in patients with operable, high-risk, localized urothelial carcinoma of the upper urinary tract. iNDUCT - GETUG V08

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nimes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-11-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Astra Zeneca grant / CHU NIMES

External identifiers

EU CT number

2024-516077-72-02

EudraCT number

2020-001028-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess in each cohort and independently the pathological complete response (ypT0) rate of a combination therapy with neoadjuvant durvalumab and chemotherapy (Gemcitabine/Cisplatin or Carboplatin) before surgery in patients with high-risk, localized, non-metastatic urothelial carcinoma of the upper tract.

Secondary objectives 3

1. In each cohort and independently: To assess pathological partial response rate to treatment.
2. In each cohort and independently : To assess the safety and tolerability to treatment.
3. In each cohort and independently: To evaluate overall survival, bladder recurrence, dissemination at two years follow-up.

Conditions and MedDRA coding

The patient has a histologically-confirmed (ureteroscopic biopsy) or cytologically(urine cytology)-confirmed diagnosis of high-grade urothelial carcinoma of the renal pelvis or ureter.

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. • The patient has a histologically-confirmed (ureteroscopic biopsy) or cytologically(urine cytology)-confirmed diagnosis of high-grade urothelial carcinoma of the renal pelvis or ureter. Presence of divergent histologies (i.e. squamous-cell tumor, adenocarcinoma, small cell carcinoma, micropapillary variant) may be acceptable provided that there is an important prevalence (> 90%) of urothelial component.
2. • Presence of either: o High-grade disease on ureteroscopic tumor biopsy OR o High-grade disease on urine cytology AND infiltrative aspect of renal pelvis/ureteral wall on CT imaging (presence of hydronephrosis will be considered invasive by definition) with negative cystoscopy. o In the absence of histological evidence, the opinion of the multidisciplinary consultation meeting (RCP) will prevail for the analysis of the imaging and the potential inclusion of the patient in the study
3. • The patient is at least 18 years old. Patients older than 70 years will be evaluated for fragility with G8 score (Soubeyran et al. 2014). Patients with a G8 score of less than 14 will not be included in the study.
4. • Body weight > 30 Kg.
5. • No prior systemic therapies.
6. • Patient must be eligible to radical nephroureterectomy surgery
7. • ECOG performance status 0 to 1.
8. • M0 No or N1 disease on CT scan.

Exclusion criteria 7

1. • Concomitant diagnosis of muscle invasive or in situ or high grade non muscle invasive urothelial carcinoma of the bladder.
2. • Evidence of NYHA functional class III or IV heart disease.
3. • Serious intercurrent medical or psychiatric illness, including serious active infection.
4. • Concomitant use of any other investigational drugs.
5. • Diagnosis of immunodeficiency or received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration.
6. • Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
7. • History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. In each cohort and independently the rate of patients who achieved a pathological complete response (PCR) after surgery will be assessed. Pathological complete response (PCR) is defined as no residual signs of viable tumor cells in tissue samples removed during surgery after treatment (yPT0). To find out if there is a pathologic complete response, a pathologist will perform an evaluation of the tissue samples under a microscope to see if there are still cancer cells left after the treatment.

Secondary endpoints 3

1. In each cohort and independently: Rate of patients showing pathological partial response (PaR). PaR is defined as downstaging to neoadjuvant pathologic stage groups ≤ ypT1N0M0 (ypT0-Ta-Tis/T1 disease). The rate of patients with PaR will be calculated on the subpopulation of patients with ureteroscopic biopsy at diagnosis.
2. In each cohort and independently: Assessment of safety and tolerability by analysing and interpreting Common Terminology Criteria for Adverse Event (CTCAE) until surgery using the National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) listing of CTCAE (NCI CTCAE V5.0).
3. In each cohort and independently:The overall survival, bladder recurrence, dissemination will be collected at 2 years follow-up 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 Nimes

Sponsor organisation

Centre Hospitalier Universitaire De Nimes

Address

Place Du Professeur Robert Debre

City

Nimes

Postcode

30900

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

Pr Stéphane DROUPY

Public contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

Pr Stéphane DROUPY

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 7 files

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