Avelumab Plus Carboplatin-gemcitabine in Urothelial Carcinoma

NCT03390595 | Completed Phase 2 DMC

• 2 other identifiers: MS100070_01602017-004260-36
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 15

Brief Summary

Phase II Multicentre, randomized, open-label study to evaluate the safety and efficacy of avelumab with gemcitabine/carboplatin versus gemcitabine/carboplatin alone in patients with unresectable or metastatic urothelial carcinoma (UC) who have not received prior systemic therapy and who are ineligible to receive cisplatin-based therapy.

Conditions

Metastatic Urothelial Cancer

Keywords

Urothelial carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The ORR is defined as the sum of the complete and partial responses (CR+PR), (according to Response Evaluation Criteria in Solid Tumours \[RECIST criteria v1.1\] and iRECIST).

  24 months

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  24 months

• Overall Survival (OS)

  24 months

• Duration of Response (DoR)

  24 months

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  24 months

Other Outcomes (3)

• Analysis of pathologic resistance mechanisms to treatment combination

  24 months

• Analysis of immunologic resistance mechanisms to treatment combination

  24 months

• Analysis of genomic resistance mechanisms to treatment combination

  24 months

Study Arms (2)

Avelumab plus gemcitabine/carboplatin

EXPERIMENTAL

2 cycles of induction avelumab 10mg/kg every 2 weeks followed by 6 cycles of carboplatin/gemcitabine plus avelumab (carboplatin 5AUC day +1, gemcitabine 1000mg/m2 day +1 and +8 and avelumab 10mg/kg day +15) every 3 weeks followed by avelumab monotherapy 10mg/kg every 2 weeks until progressive disease or intolerance.

Combination Product: avelumab 10mg/kg with carboplatin/gemcitabine

Gemcitabine/carboplatin alone

ACTIVE COMPARATOR

patients will receive 6 cycles of carboplatin/gemcitabine (carboplatin 5AUC day +1, gemcitabine 1000mg/m2 day +1 and +8) every 3 weeks.

Combination Product: carboplatin/gemcitabine alone

Interventions

avelumab 10mg/kg with carboplatin/gemcitabine COMBINATION_PRODUCT

Dosage and schedule: * Avelumab 10mg/kg will be administered over 60 minutes in the experimental arm as follows: * Intravenously every 2 weeks for two cycles. * During carboplatin-gemcitabine treatment, on day +15 (carboplatin will be administered on day 1; gemcitabine on days 1 and 8), for six cycles. Intravenously every 2 weeks until progressive disease o intolerance. * Intravenously every 2 weeks until progressive disease or intolerance. * Carboplatin-gemcitabine will be administered for six cycles, every three weeks, with the following posology, according to the SmPC * Carboplatin 5AUC day +1. * Gemcitabine 1000mg/m2 day +1 and +8.

Also known as: Bavencio

Avelumab plus gemcitabine/carboplatin

carboplatin/gemcitabine alone COMBINATION_PRODUCT

•Carboplatin-gemcitabine will be administered for six cycles, every three weeks, with the following posology, according to the SmPC * Carboplatin 5AUC day +1. * Gemcitabine 1000mg/m2 day +1 and +8.

Also known as: Standard of care for UC treatment

Gemcitabine/carboplatin alone

Eligibility Criteria

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

You may qualify if:

• The patient has given written informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study.
• The patient has histologically confirmed unresectable UC (T4b, any N; or any T, N2-3) or metastatic (M1, Stage IV) UC of the urinary tract, including renal pelvis, ureters, urinary bladder, and urethra
• No prior systemic therapy for inoperable locally advanced or metastatic UC. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo radiation for UC, a treatment-free interval \>12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting.
• Ineligible ("unfit") for cisplatin-based chemotherapy as defined by any one of the following criteria:
• Impaired renal function (GFR \<60 mL/min)
• ECOG performance status of 2
• Grade ≥2 hearing loss (measured by audiometry) or ≥25 dB at two contiguous frequencies
• Grade ≥2 peripheral neuropathy \* Criteria 4a and b are mutually exclusive: those patients with ECOG 2 won't be allowed to have an impaired renal function. For rest of the criteria, several of them may coexist.
• The patient has at least one measurable tumour lesion (measurable disease, as defined by the RECIST criteria v1.1). If all sites of measurable disease have been irradiated, one site must have demonstrated growth after irradiation.
• Age ≥18 years.
• ECOG PS 0-2.
• Life expectancy of at least 12 weeks.
• Adequate hematologic, hepatic, and renal function, defined by:
• Platelet count ≥100 x10\^9/L.
• Hemoglobin ≥ 9 g/dL (may have been transfused).

You may not qualify if:

• Women who are currently pregnant or breast-feeding.
• 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.
• Patients who had undergone major surgery, radiation therapy or treatment with chemotherapy or any investigational agent within 28 days prior to Study day 1.
• Evidence of severe or uncontrolled systemic disease or any concurrent condition (including uncontrolled diabetes mellitus) which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol.
• History of another neoplasm. However, patients with prior history of either non-metastatic non melanoma skin cancers; carcinoma in situ of the cervix; or cancer cured by surgery, small field radiation or chemotherapy ≥3 years prior to randomisation; or treated patients with early stage and low risk prostate cancer (≤pT2 N0 M0, Gleason ≤6 and Prostate-specific antigen \[PSA\] ≤0.5 ng/mL) at study entry will be eligible.
• Prior allogeneic stem cell or solid organ transplantation, or active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. However, patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
• Current use of immunosuppressive medication, EXCEPT for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
• Systemic corticosteroids at doses ≤10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• History of pulmonary fibrosis.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrolment), myocardial infarction (\< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
• Active tuberculosis.

Sponsors & Collaborators

• Associació per a la Recerca Oncologica, Spain: lead
• Merck, S.L., Spain: collaborator
• Pivotal S.L.: collaborator

Study Sites (15)

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

Location

Instituto Catalán de Oncología (ICO L'Hospitalet) - H. Durán i Reynals

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Fundación Althaia - Xarxa Assistencial Univ. de Manresa

Manresa, Barcelona, 08243, Spain

Location

Hospital Universitario Parc Tauli

Sabadell, Barcelona, 08208, Spain

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clìnic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28026, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

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  RESULT

Related Links

• APRO Website

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

avelumab; Carboplatin; Gemcitabine; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Joaquín Bellmunt, MD, PhD

  Hospital del Mar

  PRINCIPAL INVESTIGATOR

• Alejo Rodríguez-Vida, MD, PhD

  Hospital del Mar

  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: December 21, 2017
• First Posted: January 4, 2018
• Study Start: May 17, 2018
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)