Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Atezolizumab 1200 mg intravenous infusion every 3 weeks for a total of 6 doses combined with External Beam Radiation Therapy (EBRT) (dosage: 60 Gy in 30 fractions overs 6 weeks at 2Gy/day)

intravenous infusion of 1.200 mg of Atezolizumab administered intravenously every 3 weeks for a total of 6 doses

Atezolizumab Injection [Tecentriq]

60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2 Gy/day

External Beam Radiation Therapy (EBRT)

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with localized muscle-invasive bladder cancer treated with a selective multimodality bladder conservative approach.

STUDY DESIGN:

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder.

The bladder preserving therapy include combined modality therapy with:

STUDY TREATMENTS:

Investigational product (atezolizumab/Tecentriq ®):

* Route of administration: intravenous infusion.
* Duration of treatment: 16 weeks.
* Dosage: 1.200 mg intravenous every 3 weeks for a total of 6 doses. Atezolizumab is supplied as atezolizumab 1200 mg/20 mL vials (60 mg/mL) solution for intravenous infusion. After dilution, one mL of solution should contain approximately 4.4 mg of atezolizumab (1,200 mg/270 mL).

External Beam Radiation Therapy (EBRT): radiation

* Duration of treatment: 6 weeks
* Dosage: 60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2Gy/day

STUDY POPULATION:

Adult patients (aged ≥18 years) with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-T4a who are not candidates for radical cystectomy by medical reasons, refusal or patient´s choice.

A total of 39 patients are estimated to be included in the study.

OBJECTIVES:

Primary objective:

The primary objective of the study is to determine the efficacy of atezolizumab concurrent with radiotherapy in terms of pathological complete response defined as a response of grade 5 according to Miller and Payne criteria in patients with muscle-invasive bladder cancer treated with bladder preservation intent.

Secondary objectives:

* To evaluate overall survival (OS).
* To evaluate disease specific survival (DSS).
* To evaluate disease free survival (DFS).
* To evaluate bladder intact disease-free survival (BIDFS).
* To calculate the number of patients with muscle invasive and non-muscle invasive local failure (LF).
* To determine the rate of distance metastases defined as the percentage of patients who develop metastases.
* To determine to the rate of patients with bladder preserved.
* To determine to the rate of immediate or late salvage cystectomy.
* The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy.

Exploratory objectives:

* To determine the predictive role of the expression of PD-1 / PD-L1 and CD8 in terms of pCR, OS and DFS in bladder cancer patients treated with atezolizumab plus radiotherapy.
* The correlation between the levels of IFN-γ, interleukin 6 (IL-6), interleukin 18 (IL-18), or ITAC (also called CXCL11 or IP-9) and the efficacy parameters (pCR, OS and DFS) of the treatment with atezolizumab plus radiotherapy.

STUDY VISITS AND PROCEDURES:

The study includes the following visits:

* Screening: within the 28 days prior to starting the study treatment.
* Baseline visit: the first day of cycle 1
* Visits over the treatment period (16 weeks ± 7 days): from administration of the first dose of the study treatment to the administration of the last dose of atezolizumab or withdrawal from the treatment. Treatment will consist of the administration of atezolizumab at 1,200 mg intravenous every 3 weeks for 6 cycles
* Post-treatment follow-up: includes the biopsy and safety visit 1-2 months after the last dose of atezolizumab and a subsequent 5 years follow-up period after.
* End of study visit/ Early termination: In patients who end the study follow-up or prematurely withdraw from the study

Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer

Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer (Study ATEZOBLADDERPRESERVE)

Response of grade 5 according to Miller and Payne criteria

Time from the date of the beginning of protocol therapy to the date of death due to any cause

Time from start of treatment to the date of having evidence of distant metastases, nodal recurrence or recurrence within the radiotherapy field that could be salvaged in a curative fashion, what happens first

Time from the date of start of protocol therapy to the date of recurrence of muscle invasive or non-invasive bladder carcinoma or metastases, what happens first

Time from the date of initiation of protocol therapy until the development of MIBC recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death or cystectomy, what happens first

defined as patients that do not achieve a pCR defined as a response of grade 5 according to Miller and Payne criteria and documented tumour recurrence after pCR

Percentage of patients who develop distant metastases. Defined as lymphonodal involvement above the bifurcation of the iliac vessels or in inquinal regions and metastases resulting from hematogenous spread

Rate of patients with bladder preserved at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab

Immediate will be evaluated at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab and late will be evaluated during the follow-up

Collection of any adverse events and serious adverse events

Roche Farma, S.A

Dynamic Science S.L.

Spanish Oncology Genito-Urinary Group

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Bevacizumab

Angiogenesis Inhibitors

Growth Inhibitors

Radiotherapy will be given in combination with atezolizumab and bevacizumab. The patient will be initially treated with atezolizumab and bevacizumab after enrollment. Radiotherapy will be administered to the metastases 1-2 weeks after the completion of the first intravenous injection of atezolizumab and bevacizumab, in the mode of multifocal stereotactic radiotherapy, with a planned total dose to the planned target volume of 25-50 Gy in five divided doses of 5-10 Gy/fraction. Systemic therapy could be continued 48 hours after completion of radiotherapy.

Multifocal Stereotactic Radiotherapy

Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle

Bevacizumab will be administered by IV, 10 mg/kg on day 1 of each 21 day cycle

Lu Wang

Ti Zhang

Lu Wang, M.D.

This is An Open-label, Single-arm Exploratory Study to determine the efficacy and safety of Multifocal Stereotactic Radiotherapy Combined with Atezolizumab and Bevacizumab in the Treatment of Metastatic Hepatocellular Carcinoma

Efficacy and Safety of T+A+RAD in HCC

Efficacy and Safety of Multifocal Stereotactic Radiotherapy Combined With Atezolizumab and Bevacizumab in the Treatment of Metastatic Hepatocellular Carcinoma: An Open-label, Single-arm Exploratory Study

Percentage of Participants with Objective Response According To Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

time interval between objective response to progression

From screening to the first occurrence of disease progression from any cause up to end of study

From screening to the first occurrence of disease progression or death from any cause up to end of study

From screening to death from any cause up to end of study

Roche Pharma AG

Fudan University

Head of liver surgery department

Symptoms and General Pathology

Uterine Cervical Neoplasms

Recurrence

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Pharmaceutical Solutions

Pembrolizumab

9 mg VB10.16 via i.m. needle free injections in the deltoid muscles and quadricep or gluteus muscle.

Placebo will be given via IV infusions.

9 mg VB10.16 via i.m. needle free injections in the deltoid muscles and quadricep or gluteus muscle.

Atezolizumab will be given via IV infusions.

Intramuscular (i.m.) administrations of VB10.16 every 3 weeks (Q3W) during a 12-week induction period, followed by a maintenance period with administrations every 6 weeks (Q6W) from Week 13 until Week 49.

A total of up to 11 i.m. administrations will be given. VB10.16 will be administered via Pharma Jet® Stratis 0.5 mL needle free injection system.

VB10.16

Intravenous (IV) infusions of atezolizumab (saline solution) every 3 weeks.

Intravenous (IV) infusions of placebo (saline solution) every 3 weeks.

Placebo

Medical Lead Officer

Senior Clinical Trial Manager

Jennifer Pierce, MD

Jill Alldrige, MD

Sharon Robertson, MD

David Bender, MD

Erin Crane, MD, MPH

Peter G Rose, MD

Ritu Salani, MD MBA

This is a multi-center study in patients with recurrent or metastatic HPV16-positive, PD-L1 positive cervical cancer who has progressed during or after treatment with the first-line standard of care (pembrolizumab with chemotherapy with/without bevacizumab).

The trial is designed to investigate VB10.16 alone or in combination with the immune checkpoint inhibitor, atezolizumab.

The trial consist of 2 parts: the first part which investigates VB10.16 + placebo versus VB10.16 + atezolizumab. Approximately 30 patients will be included in each group. The goal of this part is to evaluate which of the two treatments is the best.

The second part of the study will select the best treatment from part 1 and investigate the safety and efficacy of additional 70 patients.

This is a two-arm randomized, double-blind, placebo-controlled phase 2 selection trial to evaluate the efficacy and safety of VB10.16 alone or in combination with atezolizumab in patients with HPV16-positive, PD-L1-positive, recurrent or metastatic cervical cancer who are refractory to pembrolizumab with chemotherapy with/without bevacizumab. A selection design with a margin of practical equivalence will be implemented to monitor efficacy of the two experimental arms (VB10.16 + atezolizumab vs. VB10.16 + placebo).

The trial consist of 2 parts: the first part which investigates VB10.16 + placebo versus VB10.16 + atezolizumab. Approximately 30 patients will be included in each group. The goal of this part is to evaluate which of the two treatments is the superior.

The second part of the study will select the superior treatment from part 1 and investigate the safety and efficacy of additional 70 patients.

A modified randomized phase 2 selection ('pick-the-winner') design with a margin of practical equivalence will be implemented to monitor efficacy of the two individual arms, and to decide which of the two arms that may be continued further based on the primary endpoint of confirmed ORR.

Efficacy and Safety of VB10.16 Alone or in Combination With Atezolizumab in Patients With Advanced Cervical Cancer.

A Two-Arm Randomized, Double-Blind, Placebo-Controlled Phase 2 Selection Trial to Evaluate the Efficacy and Safety of VB10.16 Alone or in Combination With Atezolizumab in Patients With HPV16-Positive, PD-L1-positive, Recurrent or Metastatic Cervical Cancer Who Are Refractory to Pembrolizumab With Chemotherapy With/Without Bevacizumab.

Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1 as assessed by blinded independent central review (BICR).

Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1 as assessed by the investigator.

Duration of response (DOR) based upon RECIST v1.1 assessed by BICR. DOR is defined as time from the date of first documented response of confirmed CR or PR to the date of the first documented progression or death due to any cause, whichever occur first.

Duration of response (DOR) based upon RECIST v1.1 assessed by the investigator. DOR is defined as time from the date of first documented response of confirmed CR or PR to the date of the first documented progression or death due to any cause, whichever occur first.

Time to response (TTR) based upon RECIST v1.1 assessed by BICR. TTR is defined as the time from VB10.16 treatment start date to the date of first documented response of either confirmed CR or confirmed PR.

Disease Control Rate (DCR) based upon RECIST v1.1 assessed by BICR. DCR is defined as the proportion of patients who have either confirmed CR, confirmed PR, or SD as best overall response.

Duration of disease control (DODC) based upon RECIST v1.1 assessed by BICR. DODC is defined as time from the date of first documented response of confirmed CR, confirmed PR or SD to the date of the first documented progression or death due to any cause.

Progression-free survival (PFS) as assessed by BICR. PFS is defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.

Progression-free survival (PFS) as assessed by the investigator. PFS is defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.

Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.

Proportion of participants with tumor shrinkage ≥10.0% to \<30% assessed by BICR.

Proportion of participants who are progression-free and alive based upon RECIST v1.1 assessed by BICR.

Proportion of participants who are alive.

Proportion of participants with molecular response defined as ≥30% decrease from baseline in HPV16 ctDNA.

Proportion of participants with molecular response defined as ≥50% decrease from baseline in HPV16 ctDNA.

Proportion of participants with treatment-emergent adverse events (TEAEs) by severity grade.

Proportion of participants with treatment-emergent serious adverse events

Proportion of participants with drug-related toxicity of CTCAE grade ≥3

Proportion of participants discontinuing treatment due to an adverse reaction.

GOG Foundation

Nykode Therapeutics ASA

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Hematologic Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Atezolizumab 1200 mg will be administrated every 3 week cycle

Blood sampling will be performed before and after 3rd cycle of atezolizumab for evaluation of tumor mutation burden

In-Jae Oh, MD, PhD

This is single arm, prospective, multi-center, cohort study to evaluate blood TMB for improved efficacy of atezolizumab in locally advanced or metastatic NSCLC at the study enrollment who failed one or more prior lines of chemotherapy including at least 1 platinum-based.

Atezolizumab is approved as the treatment of patients with locally advanced or metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy by the Ministry of Food and Drug Safety (MFDS) and the treatment is available on the National Health Insurance Service in South Korea. Patients will be treated with atezolizumab until loss of clinical benefit or unmanageable toxicity as routine practice.

In this study, the investigators will register patients who have a plan to be treated with atezolizumab as MFDS approval condition and meet study inclusion and exclusion criteria. The investigators will collect study related information during routine practice and collect blood and/or tissue(optional) samples to conduct the study.

Tumor assessment will be performed by investigator on the base of RECIST (version 1.1) and related information will be collected until disease progression for patients who have discontinued treatment. However, it will be collected until treatment discontinuation for patients who continue to receive atezolizumab following initial disease progression.

Evaluation of Blood TMB for the Efficacy of Atezolizumab [BUDDY]

Evaluation of Blood Tumor Mutation Burden (TMB) for Improved Efficacy of Atezolizumab in 2nd Line Non-small Cell Lung Cancer (NSCLC) [BUDDY]

PFS in Intention-to-treat (ITT) population and subgroups according to blood TMB and programmed cell death-1 (PDL1) status

Incidence of Treatment-related Adverse Events as assessed by CTCAE version 4

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer	NCT04186013	Bladder Cancer	Atezolizumab In... External Beam R...	18 Years -	Spanish Oncology Genito-Urinary Group
Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer	NCT04186013	Bladder Cancer	Atezolizumab In... External Beam R...	18 Years -	Spanish Oncology Genito-Urinary Group
Efficacy and Safety of T+A+RAD in HCC	NCT05396937	Hepatocellular ...	Multifocal Ster... Atezolizumab In... Bevacizumab	18 Years - 70 Years	Fudan University
Efficacy and Safety of VB10.16 Alone or in Combination With Atezolizumab in Patients With Advanced Cervical Cancer.	NCT06099418	HPV-Related Cer... HPV-Related Mal... Cervical Cancer	VB10.16 Atezolizumab In... Placebo	18 Years -	Nykode Therapeutics ASA
Evaluation of Blood TMB for the Efficacy of Atezolizumab [BUDDY]	NCT04059887	Lung Neoplasm M...	Atezolizumab In...	18 Years -	Chonnam National University Hospital
Efficacy and Safety of T+A+RAD in HCC	NCT05396937	Hepatocellular ...	Multifocal Ster... Atezolizumab In... Bevacizumab	18 Years - 70 Years	Fudan University

Spots Global Cancer Trial Database for atezolizumab injection [tecentriq]