Study of Atezolizumab Combined With Split-dose Gemcitabine Plus Cisplatin in Urothelial Carcinoma

NCT04602078 | Completed Phase 2 Results DMC

• 2 other identifiers: SOGUG-2020-IEC(VEJ)-12020-001326-65
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 12

Brief Summary

Phase II, multicenter, non-randomized, single-arm, open-label trial of atezolizumab in combination of split-doses of gemcitabine plus cisplatin in patients with locally advanced or metastatic urothelial carcinoma. The Aurea trial aims to evaluate the preliminary efficacy of atezolizumab plus split-dose gemcitabine and cisplatin (GC) for the first-line setting, in patients with histologically confirmed advanced (locally advanced and metastatic) urothelial cancer in terms of overall response rate (ORR) assessed by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary objectives include: efficacy (clinical benefit rate, duration of response, time to response, overall survival and progression-free survival); safety (frequency and severity of adverse events assessed by NCI CTCAE v5.0) and exploratory endpoints ( correlation of prognostic biomarkers/factors with efficacy and relationship between the expression of PD-L1 and microbiome with ORR and PFS). At least 66 patients will be included. The treatment schedule is as follows: Atezolizumab at a fixed dose of 1200 mg/m2 by intravenous (IV) infusion on D1 of each 21-day cycle up to disease progression, unacceptable toxicity or absence of clinical benefit. Gemcitabine 1000 mg/m2 IV on D1 and 1000 mg/m2 IV on D8 of each 21-day cycle plus Cisplatin 70 mg/m2 by IV on split-dose schedule of 35 mg/m2 on day 1 (D1) and 35 mg/m2 on day 8 (D8) for up to 6 cycles.

Conditions

Locally Advanced or Metastatic Urothelial Carcinoma

Keywords

Cancer; Bladder; Urethra; Ureter; metastatic or locally advanced

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Percentage/proportion of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the study period according to RECIST 1.1 criteria. Evaluated by Computed tomography scans (CT scan).

  Through study completion, average 2 years.

Secondary Outcomes (8)

• Duration of Response (DoR)

  Through study completion, average 2 years. CT scans for evaluation will be performed at baseline, on week 9, week 18 and then every 12 weeks (q12w) ± 1w until objective disease progression

• Time to Response (TtR)

  Through study completion, average 2 years. CT scans for evaluation will be performed at baseline, on week 9, week 18 and then every 12 weeks (q12w) ± 1w until objective disease progression as per PI's criteria or death (whichever comes first).

• Clinical Benefit Rate (CBR)

  Through study completion, average 2 years. CT scans for evaluation will be performed at baseline, on week 9, week 18 and then every 12 weeks (q12w) ± 1w until objective disease progression as per PI's criteria or death (whichever comes first).

• Overall Survival (OS)

  Through study completion, average 2 years.

• Progression-Free Survival (PFS)

  Through study completion, average 2 years. CT scans for evaluation will be performed at baseline, on week 9, week 18 and then every 12 weeks (q12w) ± 1w until objective disease progression as per PI's criteria or death (whichever comes first).

Other Outcomes (2)

• Progression Free Survival Measured by RECIST 1.1 in Patients Grouped According to Their PD-L1 Expression

  PD-L1 expression measured at the end of the trial. PFS assessed Through study completion, average 2 years

• ORR Measured by RECIST 1.1. in Patients Grouped According to Their PD-L1 Expression

  PD-L1 expression measured at the end of the trial. ORR assessed Through study completion, average 2 years

Study Arms (1)

AUREA single-arm

EXPERIMENTAL

Atezolizumab (1200 mg) intravenously administered every 21 days (one cycle) up to disease progression, unacceptable toxicity or absence of clinical benefit. Gemcitabine 1000 mg/m2 IV on D1 and 1000 mg/m2 IV on D8 of each 21-day cycle plus Cisplatin 70 mg/m2 by IV on split-dose schedule of 35 mg/m2 on day 1 (D1) and 35 mg/m2 on day 8 (D8) for up to 6 cycles.

Drug: Atezolizumab 1200 mg/m2; Drug: Gemcitabine 1000 mg/m2; Drug: Cisplatin 70 mg/m2

Interventions

Atezolizumab 1200 mg/m2 DRUG

Fixed dose of 1200 mg/m2 by intravenous (IV) infusion on D1 of each cycle up to disease progression, unacceptable toxicity or absence of clinical benefit.

Also known as: Tecentriq

AUREA single-arm

Gemcitabine 1000 mg/m2 DRUG

Gemcitabine 1000 mg/m2 IV on D1 and 1000 mg/m2 IV on D8 of each 21-day cycle for up to 6 cycles.

AUREA single-arm

Cisplatin 70 mg/m2 DRUG

Cisplatin 70 mg/m2 by IV on split-dose schedule of 35 mg/m2 on day 1 (D1) and 35 mg/m2 on day 8 (D8) for up to 6 cycles.

AUREA single-arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects ≥ 18 years old.
• Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
• Patients with histologically documented, locally advanced (T4B, any N; or any T, N2-3) or metastatic urothelial carcinoma (M1, Stage IV)\*.
• \*Also termed transitional cell carcinoma (TCC) or Urothelial Cell Carcinoma (UCC) of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra).
• Patients should not be eligible (unfit) for full dose of cisplatin, in the investigator's judgement, based on:
• a. Age older than 70 years. b. Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 2 or Karnofsky PS of 60 - 70% (only 15 patients will be included with ECOG 2). c. Measured creatinine clearance (ClCr) \> 30 and \< 60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for the determination of creatinine clearance:
• Males:
• Creatinine Clearance (CL) (mL/min) = Weight (kg) × (140 - Age) 72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min) =
• Weight (kg) × (140 - Age) ×0.85 72 x serum creatinine (mg/dL) d. Any other reason the physician considers but should specify in the Case Report Form (CRF) and discussed with the PI.
• At least one measurable lesion through radiographic tumor evaluation (CT scan or magnetic resonance imaging/MRI) as defined by RECIST version 1.1, that has not been previously irradiated within 4 weeks prior to the study enrolment.
• Patients with adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL.
• Absolute neutrophil count (ANC) \> 1500 per mm

You may not qualify if:

• Prior treatment with any immune checkpoint inhibitor therapy (e.g., CTLA4, PD-1, or PD-L1 targeting agent).\*
• Presence of active second malignancy and/or prior malignancy in the last 2 years is allowed except for the following:
• adequately treated basal cell or squamous cell skin cancer,
• adequately treated Stage I or II cancer from which the patient is currently in complete remission per investigators' clinical judgment.
• Active or prior documented autoimmune disease within the past 2 years. Note:
• Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g.., Crohn's disease and ulcerative colitis).
• History of allogeneic organ transplant.
• Subjects having a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior to the first dose of trial treatment.
• Current or prior use of immunosuppressive medication within 7 days prior to enrolment, except the following:
• a. Intranasal, inhaled, topical steroids, or local steroid injections i. Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent; ii. Steroids as premedication for hypersensitivity reactions
• c. Clinically significant hematemesis or hemoptysis of \> 0.5 teaspoon (\> 2.5 ml) of red blood or history of other significant bleeding within 3 months before treatment.
• d. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
• e. Lesions invading major pulmonary blood vessels.
• f. Other clinically significant disorders such as: i. Active infection requiring systemic treatment, infection with human immunodeficiency virus or acquired immunodeficiency syndrome-related illness, or chronic hepatitis B or C infection.

Sponsors & Collaborators

• Spanish Oncology Genito-Urinary Group: lead
• Roche Farma, S.A: collaborator

Study Sites (12)

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

ICO Hospitalet- Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Provincial de Castellón

Castellon, 12002, Spain

Location

Hospital Universitario de Jaén

Jaén, Spain

Location

Complejo Hospitalario Universitario Insular Marterno Infantil

Las Palmas de Gran Canaria, 35016, Spain

Location

Hospital Clínico Universitario San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Complejo Hospitalario Universitario Ourense

Ourense, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Son Llàtzer

Palma de Mallorca, 07198, Spain

Location

Hospital Virgen de la Salud

Toledo, Spain

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Neoplasms; Neoplasm Metastasis

Interventions

atezolizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: A responsible person designated by the Sponsor
• Organization: Spanish Oncology GenitoUrinary Group (SOGUG)

investigacion@mfar.net

0034934344412

Study Officials

• Guillermo Velasco, M.D., Ph.D.

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 26, 2020
• Study Start: December 23, 2020
• Primary Completion: February 2, 2024
• Study Completion: February 2, 2024
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12)