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Bladder CarcinomaPhase 2GCISAVENCT03324282

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

A Phase 2 study testing Avelumab and GC in people with Bladder Carcinoma, run by University Hospital, Bordeaux at 13 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Carcinoma
What is being tested?
Avelumab and GC
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
13 sitesFrance
Study dates
23 Feb 2018to 14 Jan 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%;
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  • 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).
  • Calculated creatinine clearance ≥ 60 mL/min
  • Women of childbearing potential must have a negative serum βHCG or urine pregnancy test within 7 days prior to initiation of treatment; both sexually active females and males (and their female partners) patients must agree to use two methods of effective contraception one of them being a barrier method, or to abstain from sexual activity during the study, for at least 3 months after the last administration of study treatment;
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures;
  • Patient affiliated to a social security system or beneficiary of the same.

Who cannot join

  • 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;
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  • 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;
  • History of organ transplant including allogeneic stem-cell transplantation;
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3);
  • Women who are pregnant or lactating;
  • Known history of testing positive for HIV or known acquired immunodeficiency syndrome;
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

France13 sites

  • CHU de Besançon

    Besançon

  • CHU de Bordeaux

    Bordeaux

  • Institut Bergonié

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Léon Bérard

    Lyon

  • Institut Paoli Calmettes

    Marseille

  • Institut de cancérologie de l'Ouest - René Gauducheau

    Nantes

  • Hôpital Européen Georges-Pompidou, AP-HP

    Paris

  • Hôpital Saint-Louis, AP-HP

    Paris

  • CHU de Poitiers

    Poitiers

  • CHU de Strasbourg

    Strasbourg

  • Institut Universitaire du Cancer de Toulouse - Oncopole

    Toulouse

  • Institut Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: Gemcitabine-cisplatin Plus Avelumab or Gemcitabine-cisplatin as First-line Treatment of Patients With Locally Advanced or Metastatic Urothelial Bladder Carcinoma (GCISAVE)

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).

Read the detailed description

Recent results in cancer research highlight the importance of immune checkpoints in the control of immune response and provide access to molecules interfering with the inhibited immune response during the development of cancer. Drugs targeted against CTLA-4, PD-1 or PD-L1 have shown efficacy in various tumor types. In locally advanced or metastatic urothelial bladder cancer (MBC), the standard first-line treatment is the association of Gemcitabine and Cisplatin (GC). Objective responses and prolonged objective responses have been reported with monoclonal antibodies against PD-1 or PD-L1 in MBC patients after failure of chemotherapy. Avelumab is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody. Avelumab treatment did not show unexpected cross-toxicity with chemotherapy when studied in phase I / II in patients with different tumor types. So the combination at full doses of GC and avelumab seems appropriate.

The experimental treatment is a combination of GC and avelumab given for 6 cycles. The duration of each cycle is 3 weeks (Gemcitabine: dose of 1000 mg/m2 as an intravenous infusion over 30 minutes on Days 1 and 8 of each 21-day cycle; Cisplatin: dose of 70 mg/m2 as a slow intravenous infusion over 2 to 4 hours on Day 1 of each 21-day cycle; Avelumab: 10 mg/kg body weight administered Iv once every 3 weeks).

Patients who have received all scheduled treatments and whose disease has not progressed at the end of treatment will enter into disease follow-up. During this follow-up period, patients will have disease and safety assessments performed every 3 months. Patients will remain in follow-up for up to 1 year from last dose of treatment and will have survival follow-up.

Being tested
Avelumab, GC
Keywords
Anti PD1, Bladder carcinoma, Chemotherapy, Immunological monitoring
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

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

  • GCDrug

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

Study groups in NCT03324282
Study groupRoleWhat they receive
Arm A: GC + avelumab groupExperimentalNot described
Receives: Drug: Avelumab; Drug: GC
Arm B: GC groupActive comparatorNot described
Receives: Drug: GC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy: objective response rate with RECIST 1.1 with GC + avelumab

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

  2. Safety: proportion of severe toxicity with GC + avelumab

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

Secondary outcomes (7)

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

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

  2. Specific immunological toxicity documented and recorded using NCI CTCAE version 4.0

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

  3. Duration of response

    Measured: Up to 18 months

  4. Progression-free survival

    Measured: At 18 months in GC+avelumab treated patients

  5. Overall survival

    Measured: At 18 months in GC+avelumab treated patients

  6. GC+avelumab efficacy according to the expression of PD-L1 at the tumor site

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

  7. GC+avelumab efficacy according to the immune infiltrate populations at the tumor level and/or the tumor surroundings

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2017
  2. Study start23 Feb 2018
  3. Primary completion31 Dec 2021
  4. Study completion14 Jan 2022

Why it stopped: ANSM's refusal to validate ATU requests for avelumab in bladder cancer, Decrease in recruitment, Most investigators would like to offer avelumab for maintenance, Absence of benefit to the chemo-immuno combination (pembro+gem-platinum) in phase III

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03324282
Sponsor's protocol ID
CHUBX 2016/33
Other IDs
2017-002087-40, 2017
Acronym
GCISAVE
Status last verified
Apr 2022
First submitted
19 Oct 2017
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32620210

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab and GC in people with Bladder Carcinoma, run by University Hospital, Bordeaux at 13 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: ANSM's refusal to validate ATU requests for avelumab in bladder cancer, Decrease in recruitment, Most investigators would like to offer avelumab for maintenance, Absence of benefit to the chemo-immuno combination (pembro+gem-platinum) in phase III). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy: objective response rate with RECIST 1.1 with GC + avelumab (time frame: At the end of cycle 6 (each cycle is 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03324282, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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