First-line Gemcitabine/Cisplatin +/- Avelumab in Locally Advanced or Metastatic Bladder Carcinoma

NCT03324282 | Terminated Phase 2 DMC

• 1 other identifier: CHUBX 2016/33
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 13

Brief Summary

This study will assess efficacy (based on response rate) and safety (based on grade ≥ 3 severe adverse effects) of the combination Gemcitabine Cisplatin (GC) + anti-PD-L1 (avelumab) in first-line treatment for locally advanced or metastatic urothelial bladder cancer patients, after 6 cycles of treatment (or at 18 weeks if less than 6 cycles have been given, or earlier if a second line treatment is needed, before this new anticancer treatment has been started).

Conditions

Bladder Carcinoma

Keywords

Anti PD1; Bladder carcinoma; Chemotherapy; Immunological monitoring

Outcome Measures

Primary Outcomes (2)

• Efficacy: objective response rate with RECIST 1.1 with GC + avelumab

  At the end of cycle 6 (each cycle is 21 days)

• Safety: proportion of severe toxicity with GC + avelumab

  At the end of cycle 6 (each cycle is 21 days)

Secondary Outcomes (7)

• Immunological capacities in peripheral blood of GC alone and GC+avelumab groups

  During treatment and after the 6 cycles of treatment (EOT + 3, 6, 9 and 12 months

• Specific immunological toxicity documented and recorded using NCI CTCAE version 4.0

  At the end of cycle 6 (each cycle is 21 days)

• Duration of response

  Up to 18 months

• Progression-free survival

  At 18 months in GC+avelumab treated patients

• Overall survival

  At 18 months in GC+avelumab treated patients

Study Arms (2)

Arm A: GC + avelumab group

EXPERIMENTAL

Drug: Avelumab; Drug: GC

Arm B: GC group

ACTIVE COMPARATOR

Drug: GC

Interventions

Avelumab DRUG

Combination of Gemcitabin-Cisplatin and avelumab given for 6 cycles (each cycle is 21 days)

Arm A: GC + avelumab group

GC DRUG

Combination of Gemcitabin-Cisplatin given for 6 cycles (each cycle is 21 days)

Arm A: GC + avelumab group; Arm B: GC group

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent;
• Male or female, age ≥18 years at time of informed consent signature;
• Histological confirmed locally advanced (any T N2-3) or metastatic urothelial bladder carcinoma, eligible to first-line treatment (previous neo adjuvant or adjuvant treatment must have been given and stopped more than one year before);
• Evidence of progressive disease in the previous 6 months, documented by chest and/or abdominal CT-scan or MRI;
• Measurable disease according to RECIST 1.1;
• Karnofsky index ≥ 70%;
• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour specimen (infiltrative urothelial bladder carcinoma or metastasis) collected within 12 months before Cycle 1 Day 1;
• At least 3 weeks since the end of prior local intravesical treatment (BCG-therapy or ametycine) with resolution of all treatment-related toxicity to grade ≤1 (NCI CTCAE 4.0);
• Palliative local treatment is allowed if performed ≥ 2 weeks prior study entry for radiotherapy, cimentoplasty or minor surgery, and ≥4 weeks for major surgery;
• Adequate organ function as defined by the following criteria:
• Absolute White Blood Cells count (WBC) ≥ 2000 cells/mm3
• Absolute Neutrophils count (ANC) ≥ 1500 cells/mm3
• Platelets ≥100 000 cells/mm3
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).

You may not qualify if:

• Other prior first-line therapy;
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; focal radiation therapy less than 14 days prior to the first day of the first cycle;
• Other invasive malignancy within 3 years (except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast); Patient with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 7 and PSA ≤ 10ng/mL) who are treatment-naïve and undergoing active surveillance are eligible;
• Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable;
• Symptomatic central nervous system (CNS) metastases or untreated CNS metastases requiring concurrent treatment;
• Clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication;
• Uncontrolled adrenal insufficiency;
• Active chronic liver disease;
• Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study;
• Active infection requiring systemic antibiotic;
• Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines;
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication);
• Major surgery less than 28 days prior to the first day of the first cycle. Minor surgery less than 14 days prior to the first day of the first cycle;
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible;
• History of primary immunodeficiency;

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (13)

CHU de Besançon

Besançon, France

Location

CHU de Bordeaux

Bordeaux, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Institut de cancérologie de l'Ouest - René Gauducheau

Nantes, France

Location

Hôpital Européen Georges-Pompidou, AP-HP

Paris, France

Location

Hôpital Saint-Louis, AP-HP

Paris, France

Location

CHU de Poitiers

Poitiers, France

Location

CHU de Strasbourg

Strasbourg, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Gross-Goupil M, Domblides C, Lefort F, Ravaud A. Open-label randomized multi-center phase 2 study: gemcitabine cisplatin plus avelumab or gemcitabine cisplatin as first-line treatment of patients with locally advanced or metastatic urothelial bladder carcinoma: GCisAve. Bull Cancer. 2020 Jun;107(5S):eS1-eS7. doi: 10.1016/S0007-4551(20)30280-0.

  PMID: 32620210 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Alain RAVAUD, MD. PhD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: October 27, 2017
• Study Start: February 23, 2018
• Primary Completion: December 31, 2021
• Study Completion: January 14, 2022
• Last Updated: May 3, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)