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This study will evaluate the efficacy and safety of atezolizumab in combination with bevacizumab in patients with unresectable locally advanced or metastatic mucosal melanoma.
The study is divided into 2 stages. Stage I of the study is completed when 22 patients with measurable disease have been enrolled and completed ORR evaluation. If the number of responders in Stage I is more than 3, another 16 patients may be enrolled to Stage II.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atezolizumab + Bevacizumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Atezolizumab 1200 mg will be administered intravenously every 3 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) in the Full Analysis Set Analysis Population | ORR was defined as the percentage of participants with a complete response (CR) defined as disappearance of all target lesions, or partial response (PR) defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR, on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). | Up to approximately 32 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | PFS was defined as the time from the date of first treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. | Up to approximately 32 months |
| Overall Survival (OS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Center; Renal Cancer And Melanoma Department. | Beijing | 100142 | China | |||
| Fujian Provincial Cancer Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36044526 | Derived | Mao L, Fang M, Chen Y, Wei X, Cao J, Lin J, Zhang P, Chen L, Cao X, Chen Y, Guo J, Si L. Atezolizumab plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: A Multicenter, Open-Label, Single-Arm Phase II Study. Clin Cancer Res. 2022 Nov 1;28(21):4642-4648. doi: 10.1158/1078-0432.CCR-22-1528. |
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Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
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There were 20 participants who died during the follow-up period who were recorded as study completed as per the protocol.
This study was conducted at 3 centers in China.
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| ID | Title | Description |
|---|---|---|
| FG000 | Atezolizumab + Bevacizumab | Participants received 1200 mg atezolizumab by intravenous infusion every 3 weeks and/or 7.5 mg/kg bevacizumab by intravenous infusion every 3 weeks until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who transiently withheld or permanently discontinued either atezolizumab or bevacizumab may continue on single-agent therapy as long as the participants were experiencing clinical benefit in the opinion of the investigator. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intention-to-treat population is defined as all enrolled participants regardless of whether they receive any assigned study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Atezolizumab + Bevacizumab | Participants received 1200 mg atezolizumab by intravenous infusion every 3 weeks and/or 7.5 mg/kg bevacizumab by intravenous infusion every 3 weeks until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who transiently withheld or permanently discontinued either atezolizumab or bevacizumab may continue on single-agent therapy as long as the participants were experiencing clinical benefit in the opinion of the investigator. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Progression-Free Survival (PFS) | PFS was defined as the time from the date of first treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. | Full Analysis Set (FAS) is defined as all enrolled participants who receive any amount of study treatment and evaluable for efficacy endpoints. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 32 months |
|
From the first study drug to the data cutoff date: 31 August 2022 (up to approximately 32 months)
All-cause mortality reported for deaths that occurred during study based on ITT, which included all participants. Serious & other adverse events reported based on safety population, which included participants who received any amount of any component of study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Atezolizumab + Bevacizumab | Participants received 1200 mg atezolizumab by intravenous infusion every 3 weeks and/or 7.5 mg/kg bevacizumab by intravenous infusion every 3 weeks until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who transiently withheld or permanently discontinued either atezolizumab or bevacizumab may continue on single-agent therapy as long as the participants were experiencing clinical benefit in the opinion of the investigator. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Immune-mediated hepatitis | Hepatobiliary disorders | MedDRA version 25.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood lactate dehydrogenase increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 13, 2023 | Feb 2, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 12, 2020 | Feb 2, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Bevacizumab | Drug | Bevacizumab 7.5 mg/kg will be administered intravenously every 3 weeks. |
|
|
Overall survival was defined as the time from the date of first treatment to death from any cause. |
| Up to approximately 32 months |
| Duration of Objective Response (DOR) | DOR was defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 | Up to approximately 32 months |
| Disease Control Rate (DCR) | DCR was defined as the sum of a complete or partial response or stable disease rates as determined by the investigator according to RECIST v1.1. | Up to approximately 32 months |
| Percentage of Participants With Adverse Events | The percentage of participants who experienced an Adverse Event (AE) or Serious Adverse Event (SAE). Incidence, nature, and severity of Adverse Events (AE), are reported per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0). | From the first study drug to the data cutoff date: 31 August 2022 (up to approximately 32 months) |
| Fuzhou |
| 350014 |
| China |
| Zhejiang Cancer Hospital | Zhejiang | 310022 | China |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | Overall Survival (OS) | Overall survival was defined as the time from the date of first treatment to death from any cause. | Full Analysis Set (FAS) was defined as all enrolled participants who receive any amount of study treatment and evaluable for efficacy endpoints. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 32 months |
|
|
|
| Secondary | Duration of Objective Response (DOR) | DOR was defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 | Only responders (CR/PR) assessed by investigator were included in the analysis. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 32 months |
|
|
|
| Secondary | Disease Control Rate (DCR) | DCR was defined as the sum of a complete or partial response or stable disease rates as determined by the investigator according to RECIST v1.1. | Full Analysis Set (FAS) was defined as all enrolled participants who receive any amount of study treatment and evaluable for efficacy endpoints. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to approximately 32 months |
|
|
|
| Secondary | Percentage of Participants With Adverse Events | The percentage of participants who experienced an Adverse Event (AE) or Serious Adverse Event (SAE). Incidence, nature, and severity of Adverse Events (AE), are reported per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0). | Safety analysis set is defined as all enrolled participants who receive any amount of least one dose of any study treatment. | Posted | Number | Percentage of participants | From the first study drug to the data cutoff date: 31 August 2022 (up to approximately 32 months) |
|
|
|
| Primary | Objective Response Rate (ORR) in the Full Analysis Set Analysis Population | ORR was defined as the percentage of participants with a complete response (CR) defined as disappearance of all target lesions, or partial response (PR) defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR, on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). | Full Analysis Set (FAS) is defined as all enrolled participants who receive any amount of study treatment and evaluable for efficacy endpoints. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to approximately 32 months |
|
|
|
| 20 |
| 43 |
| 9 |
| 43 |
| 34 |
| 43 |
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Abdominal infection | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
|
| Hypophysitis | Endocrine disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
|
| Orbital infection | Infections and infestations | MedDRA version 25.0 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Post herpetic neuralgia | Nervous system disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Gastrointestinal perforation | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Autoimmune lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Bilirubin conjugated increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Blood bilirubin unconjugated increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Protein urine present | Investigations | MedDRA version 25.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 25.0 | Systematic Assessment | General disorders and administration site conditions |
|
| Fatigue | General disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 25.0 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version 25.0 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
|
| Percentage of participants with at least one AE by worst grade - Grade 2 |
|
| Percentage of participants with at least one AE by worst grade - Grade 3 |
|
| Percentage of participants with at least one AE by worst grade - Grade 4 |
|
| Percentage of participants with at least one AE by worst grade - Grade 5 |
|
| Percentage with at least one SAE |
|