Cisplatin, Nab-paclitaxel, Nivolumab With Radiotherapy After Resection of Non-Metastatic Muscle Invasive Bladder Cancer

NCT05203913 | Recruiting Phase 2

• 1 other identifier: 4353
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase II study, eligible patients will be treated with maximal tumor resection and then started treatment within 8 weeks. Chemotherapy, Nivolumab and radiotherapy (RT) will be started on day one. Chemotherapy will be administered weekly during radiotherapy. Radiotherapy will be performed from Monday to Friday for five weeks. Nivolumab will be administered for one year (13 infusions). Patients will have the complete tumour assessment by computed tomography scan (CT-scan) and cystoscopy up to 5 years after radiotherapy.

Conditions

Muscle-Invasive Bladder Carcinoma

Keywords

nivolumab; nab-paclitaxel; cisplatin; trimodal therapy; radiotherapy

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  Disease-free survival is defined as the rate of survival free of recurrence in pelvic nodes or bladder, or appearance of distant metastasis with data censored at the first sign of disease or second primary tumor, or death.

  From the start of therapy up to 5 years.

Secondary Outcomes (8)

• Rate of patients who require salvage cystectomy.

  From the start of therapy up to 5 years.

• Rate of locoregional Disease Free Survival.

  From the start of therapy up to 5 years.

• Median Disease Free Survival.

  From the start of therapy up to 5 years.

• Overall survival

  From the start of therapy up to 5 years.

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 during treatment with nivolumab plus cisplatin and nab-paclitaxel with concomitant RT.

  From the start of therapy up to 30 days after the end of radiotherapy.

Other Outcomes (2)

• Median Disease Free Survival by PD-L1 expression.

  From the start of therapy up to 5 years.

• Median Disease Free Survival by PI3KCA mutations

  From the start of therapy up to 5 years.

Study Arms (1)

Experimental arm

EXPERIMENTAL

This arm consists in treatment with cisplatin + nab-paclitaxel + nivolumab during radiotherapy on bladder followed by nivolumab alone after the end of radiotherapy

Drug: Nivolumab; Drug: Nab paclitaxel; Drug: Cisplatin; Radiation: Radiotherapy

Interventions

Nivolumab DRUG

The recommended dose for nivolumab is 480 mg administered as 30 minutes IV infusions every 28 days for 13 infusions.

Also known as: Opdivo

Experimental arm

Nab paclitaxel DRUG

The recommended dose for nab-paclitaxel is 60 mg per square meter administered as 30 minutes IV infusions every 7 days (weekly), during the radiotherapy period.

Also known as: Abraxane

Experimental arm

Cisplatin DRUG

The recommended dose for cisplatin is 20 mg per square meter administered as 60 minutes IV infusions every 7 days (weekly), during the radiotherapy period.

Also known as: CDDP

Experimental arm

Radiotherapy RADIATION

Radiotherapy will be delivered over approximately 5 weeks.The total radiotherapy dose will be: 60 Gray in 25 fractions over 5 weeks on original bladder tumour, 50 Gray in 25 fractions over 5 weeks on whole bladder and pelvic nodes if included, administered as concomitant boost. Radiation therapy will be delivered once daily (Monday-Friday) continuously without a planned break for tumour response assessment during treatment.

Also known as: RT

Experimental arm

Eligibility Criteria

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

You may qualify if:

• years old or older
• Histologic diagnosis of predominantly urothelial carcinoma of the bladder. Focal differentiation allowed other than small cell histology.
• Stage T2-T3 N0M0 (AJCC-TNM version 6) based on trans-urethral resection of bladder tumor (TURBT), CT or MRI imaging, +/- bimanual examination under anaesthesia.
• FDG-PET within 6 weeks from the start of treatments, showing no evidence of lymph nodes or metastatic disease.
• Attempt of complete trans urethral resection of bladder tumour (TURBT) within 56 days (8 weeks) prior to the start of chemoradiotherapy. If TURBT was performed \> 8 weeks prior but a recent cystoscopy shows no residual disease, then a repeat TURBT is not necessary.
• Life expectancy greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 1 or better
• Another primary cancer is allowed only if treated with curative intent at least 3 years prior to enrolment without evidence of recurrence or if the untreated cancer is clinically indolent (e.g., lower risk prostate cancer).
• Patients must be considered able to tolerate systemic chemotherapy combined with pelvic intensity-modulated radiation therapy (IMRT) by the joint agreement of the participating radiation oncologist and medical oncologist.
• Able and willing to give written informed consent.
• For women of childbearing potential (WOCBP), study participants must use a contraceptive method that is highly effective (with a failure rate of \< 1% per year) for at least 5 months after the last dose of study intervention. Men receiving any study drug and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 6 months after the last dose of chemotherapy with cisplatin or nab-paclitaxel.
• The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care. Acceptable methods are oral contraceptives, hormonal implants, hormonal patches, IDU, Diaphragm with spermicides, cervical cape with spermicide, and condom with spermicide.
• Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment:
• Total bilirubin ≤1∙5 × the upper limit of normal (ULN).
• Alanine aminotransferase and aspartate aminotransferase ≤2 × ULN (≤5 × ULN for patients with liver involvement of their cancer).

You may not qualify if:

• Prior systemic therapy for other urothelial tumours.
• Prior RT to the pelvis
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to enrolment.
• Malignancies other than urothelial cancer within 3 years prior to Cycle 1, Day 1:
• Patients with localized lower risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤ 7, and PSA at prostate cancer diagnosis ≤ 20 ng/mL \[if measured\]) treated with radical prostatectomy and without prostate-specific antigen (PSA) recurrence are eligible.
• Patients with lower risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 7 and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
• Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death \<5% at 5 years) are eligible provided they meet all the following criteria:
• Malignancy treated with expected curative intent (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated surgically with curative intent) No evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers.
• Pre-existing medical conditions precluding treatment (e.g., previous history of immune-related adverse reactions, pneumonitis, colitis, etc.)
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
• Active tuberculosis
• For women of childbearing potential (WOCBP), study participants must use a contraceptive method that is highly effective (with a failure rate of \< 1% per year) for at least 5 months after the last dose of study intervention. Men receiving any study drug and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 6 months after the last dose of chemotherapy with cisplatin or nab-paclitaxel.
• Acceptable methods are oral contraceptives, hormonal implants, hormonal patches, IDU, Diaphragm with spermicides, cervical cape with spermicide, and condom with spermicide.
• Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor \[TNFR\] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Roberto iacovelli

Roma, 00168, Italy

RECRUITING

MeSH Terms

Interventions

Nivolumab; Taxes; Albumin-Bound Paclitaxel; Cisplatin; Radiotherapy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Roberto Iacovelli, MD, PhD

  Fondazione Policlinico Universitario A. Gemelli IRCCS. Largo A. Gemelli 8, 00168 Rome, Italy.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto Iacovelli, MD, PhD

CONTACT

+390630157373; roberto.iacovelli@policlinicogemelli.it

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: November 29, 2021
• First Posted: January 24, 2022
• Study Start: May 1, 2023
• Primary Completion: December 15, 2025
• Study Completion: June 15, 2026
• Last Updated: October 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)