Safety & Efficacy of Durvalumab+Neoadjuvant Chemotherapy for High-risk Urothelial Carcinoma of the Upper Urinary Tract

NCT04617756 | Recruiting Phase 2

• 1 other identifier: CIVI/2018/NH-1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 9

Brief Summary

Following radical nephrectomy (RNU) for upper tract urothelial carcinoma (UTUC) most patients face a poor prognosis. Indeed, patients who have undergone RNU for UTUC have 5-year recurrence-free and cancer specific survival probabilities of 69% and 73% respectively. The primary objective of this study is to assess the pathological complete response rate to combination therapy with neoadjuvant durvalumab and chemotherapy (Gemcitabine/Cisplatin) before surgery in patients with high-risk, localized, non-metastatic urothelial carcinomas of the upper tract.

Conditions

Urothelial Carcinoma; Cancer

Keywords

Durvalumab; Gemcitabine; Cisplatin; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Pathological complete response in Cohort 1

  For Cohort 1 (patients on treatment combining Durvalumab and Gemcitabine associated with Cisplatin) the rate of patients with pathological complete response will be calculated and presented with associated 95% confidence interval on the subpopulation of patients with ureteroscopic biopsy at diagnosis.Pathological complete response is defined as no residual signs of viable tumor cells in tissue samples removed during surgery after treatment. 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.

  Week 14 - 18

• Pathological complete response in Cohort 2

  For Cohort 2 (patients on treatment combining Durvalumab and Gemcitabine associated with Carboplatin) the rate of patients with pathological complete response will be calculated and presented with associated 95% confidence interval on the subpopulation of patients with ureteroscopic biopsy at diagnosis.Pathological complete response is defined as no residual signs of viable tumor cells in tissue samples removed during surgery after treatment. 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.

  Week 14 - 18

Secondary Outcomes (90)

• Partial pathological response in Cohort 1

  Week 3

• Partial pathological response in Cohort 2

  Week 3

• Partial pathological response in Cohort 1

  Week 6

• Partial pathological response in Cohort 2

  Week 6

• Partial pathological response in Cohort 1

  Week 9

Other Outcomes (10)

• Tumor staging in Cohort 1

  Just before surgery at weeks 14 to 18

• Tumor staging in Cohort 2

  Just before surgery at weeks 14 to 18

• Results of biopsy on tissue specimens after surgery in Cohort 1

  After surgery at weeks 14 to 18

Study Arms (1)

Durvalumab+Gemcitabine/Cisplatin or with Gemcitabine/Carboplatin

EXPERIMENTAL

This is a single arm including 2 different cohorts : Cohort 1 includes patients on 40mg/ML Gemcitabine/50mg Cisplatin used in combination with 50 mg/mL of intravenous Durvalumab (laboratory code MEDI 4736) every 3 weeks for a total of 4 cycles and Cohort 2 includes patients on 40mg/ML Gemcitabine/450mg Carboplatin used in combination with 50 mg/mL of intravenous Durvalumab (laboratory code MEDI 4736) every 3 weeks for a total of 4 cycles..

Drug: Patients receiving neoadjuvant therapy before radical nephrectomy

Interventions

Patients receiving neoadjuvant therapy before radical nephrectomy DRUG

Chemotherapy using either a combination of Gemcitabine/Cisplatin and neoadjuvant immunotherapy therapy with Durvalumab (MEDI 4736) or Chemotherapy with either Gemcitibine/Carboplatin and neoadjuvant immunotherapy therapy with Durvalumab (MEDI 4736)

Durvalumab+Gemcitabine/Cisplatin or with Gemcitabine/Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has been correctly informed and has given signed consent.
• Patient is covered by a health insurance scheme.
• Patients aged over 70 must have a G8 score (Soubeyran et al. 2014) of at least 14.
• Patient's body weight must be over 30kg
• Patient has high-grade urothelial carcinoma of the renal pelvis or ureter confirmed histologically (uteroscopic biopsy) or cytologically (urine cytology).
• Presence of EITHER high-grade disease on the uteroscopic tumor biopsy
• OR Presence of high-grade disease on urine cytology AND infiltrative aspect of renal pelvis/ ureteral wall on the CT scan (presence of hydronephrosis will be considered invasive by definition) with negative cystoscopy.
• No prior systemic therapies.
• ECOG performance status 0 to 1.
• M0 No or N1 disease on CT scan.
• Required initial laboratory values :
• Absolute neutrophil count of over 1500 cells/mm²
• Platelet count of over 100,000 cells/mm3
• Hemoglobin over 9.0 g/dL
• Bilirubin below 1.5 times the Upper Limit of Normal for the institution

You may not qualify if:

• The patient is participating in another interventional trial;
• or is under judicial protection, or is an adult under guardianship
• or refuses to sign the consent;
• or it is impossible to correctly inform the patient.
• The patient is pregnant or breastfeeding.
• Concomitant diagnosis of muscle invasive or in situ or high grade non muscle invasive urothelial carcinoma of the bladder.
• Evidence of NYHA functional class III or IV heart disease.
• Serious intercurrent medical or psychiatric illness, including serious active infection.
• Concomitant use of any other investigational drugs.
• Diagnosis of immunodeficiency or received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration.
• Additional malignancy within last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer that has undergone potentially curative therapy, stable (as defined by PSA change, checked within 30 days) and untreated very low-risk or low-risk prostate cancer defined by current NCCN guidelines. Previous or concomitant history of non-muscle invasive bladder cancer is acceptable.
• 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. NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception. Subjects that require systemic corticosteroids at physiologic doses not exceed 10mg/day of prednisone or its equivalent would not be excluded from the study. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
• History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C.
• Live vaccine received within 30 days prior to the first dose of trial treatment.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead
• Pitié-Salpêtrière Hospital: collaborator
• Hôpital Bichat-Claude Bernard, 75018 Paris: collaborator
• Hopital Foch 92151 Suresnes: collaborator
• Institut Paoli-Calmettes: collaborator
• European Georges Pompidou Hospital: collaborator
• Saint-Louis Hospital, Paris, France: collaborator
• Centre Hospitalier Lyon Sud: collaborator
• Center Eugene Marquis: collaborator
• IUCT ONCOPOLE: collaborator

Study Sites (9)

Hôpital Bichat-Claude Bernard

Paris, Paris Cx 20, 75018, France

RECRUITING

Institut Paoli Calmette

Marseille, 13009, France

RECRUITING

Hôpital Saint Louis

Paris, 75010, France

RECRUITING

Hôpital Pitié Salpétrière

Paris, 75013 Paris, France

RECRUITING

Hôpital Européen Georges Pompidou

Paris, 75015, France

RECRUITING

Centre hospitalier Lyon Sud

Pierre-Bénite, 69310, France

RECRUITING

Centre Eugène Marquis

Rennes, 35042, France

RECRUITING

Hôpital Foch

Suresnes, 92151, France

RECRUITING

Iuct Oncopole

Toulouse, 31059, France

RECRUITING

Related Publications (2)

• Houede N, Chevallier T, Audenet F, Thibault C, Neuzillet Y, Abraham C, Masson-Lecomte A, Gauthier H, Gravis G, Pignot G, Tartas S, Ruffion A, Pouessel D, Roumiguie M, Laguerre B, Bensalah K, Xylinas E, Jaffrelot L, Droupy S, Luquiens G, Roupret M. Safety and Efficacy of Neoadjuvant Durvalumab Plus Gemcitabine/Cisplatin or Carboplatin in Patients With Operable High-Risk Upper Tract Urothelial Carcinoma: The iNDUCT-GETUG V08 Trial. J Clin Oncol. 2025 May;43(13):1578-1586. doi: 10.1200/JCO-25-00179. Epub 2025 Feb 14.

  PMID: 39951246 DERIVED

• Calleris G, Roupret M, Seisen T, Bendjeddou L, Chevallier T, Masson-Lecomte A, Thibault C, Neuzillet Y, Audenet F, Xylinas E, Houede N. Design and rationale of a single-arm phase II study of neoadjuvant Durvalumab and Gemcitabine associated with Cisplatin or Carboplatin for upper urinary tract urothelial cancer: the iNDUCT trial (NCT04617756). World J Urol. 2023 Dec;41(12):3413-3420. doi: 10.1007/s00345-023-04596-5. Epub 2023 Sep 12.

  PMID: 37698632 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Central Study Contacts

Nadine HOUEDE, Pr.

CONTACT

+33 4 66 68 33 01; nadine.HOUEDE@chu-nimes.fr

Annissa MEZGARI

CONTACT

+33 4 66 68 30 52; drc@chu-nimes.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with an estimated glomerular filtration rate equal to or over 60 ml/min./1.73² (cohort 1) will receive treatment combining Durvalumab and gemcitabine with Cisplatin. Patients with an estimated glomerular filtration rate of under 60 ml/min./1.73² and over 40 ml/min./1.73² (cohort 2) will receive treatment combining Durvalumab and gemcitabine with Carboplatin.

Study Record Dates

• First Submitted: October 28, 2020
• First Posted: November 5, 2020
• Study Start: September 29, 2021
• Primary Completion: January 1, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 30, 2023

Record last verified: 2023-05

Locations

FR (9)