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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-01221 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| P30CA015704 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase II trial studies the effectiveness of ImmunoPulse IL-12® in treating patients with Merkel cell cancer. ImmunoPulse IL-12® is the combination of intratumoral interleukin-12 gene (also known as tavokinogene telseplasmid [tavo]) and in vivo electroporation-mediated plasmid deoxyribonucleic acid [DNA] vaccine therapy (tavo-EP) administered using the OncoSec Medical System (OMS). Placing the gene for interleukin-12 into Merkel cells may help the mount an effective anti-tumor immune response to kill tumor cells.
PRIMARY OBJECTIVES:
I. To measure the effect of intratumoral injection of tavo followed by in vivo electroporation (EP) (electroporation-mediated plasmid DNA vaccine therapy) on the local expression of interleukin-12 (IL-12) in the tumor microenvironment in patients with Merkel cell carcinoma (MCC).
SECONDARY OBJECTIVES:
I. To assess the safety of tavo-EP in MCC. II. To assess the clinical efficacy of this treatment approach in MCC. III. To assess the immunologic changes resulting from this treatment approach.
OUTLINE:
Patients receive tavo intratumorally (IT) and undergo electrical discharge via OMS around the tumor site for electroporation-mediated plasmid DNA vaccine therapy on days 1, 5, and 8. Patients with unresectable disease may receive a second course of treatment in 12 weeks. Patients with localized disease proceed to definitive treatment as determined by the treating physician starting 2-4 weeks after the first injection.
After completion of study treatment, patients are followed up at weeks 4-8 (for patients who received definitive treatment) or 12 (for patients with unresectable disease) and then annually for up to 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: Tavo-EP | Experimental | Patients in Cohort A received one cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, after which they proceeded to definitive treatment (surgery and/or radiation therapy) which started between 2 and 4 weeks after the first injection. |
|
| Cohort B: Tavo-EP | Experimental | Patients in Cohort B received up to 4 cycles (3 daily treatments on Days 1, 5, and 8, per cycle) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, with 12 planned weeks between each cycle, lasting up to 12 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tavokinogene Telseplasmid (tavo) | Biological | Patients received intratumoral injection(s) of tavo. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced At Least 2-Fold Increase in Expression of IL-12 Protein in the Tumor Tissue After Intratumoral (IT) pIL-12 Injections and In Vivo Electroporation | The MAGPIX assay was used to assess differential expression of hIL-12 in patient tumor tissue before and after treatment with intratumoral (IT) tavo injections and in vivo electroporation (EP). Expression of hIL-12 was used to identify patients who met the primary endpoint of a 2-fold or higher increase in expression of hIL-12 in tumors after treatment. Fold change was taken as a comparison of hIL-12 expression at Week 3:pre-treatment, Week 6:pre-treatment, Week 8:pre-treatment, or Week 13:pre-treatment over baseline (pre- treatment). The fold change was calculated as log2 (time point/baseline). | Pre-treatment up to Week 13 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, medical treatment or procedure and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could have, therefore, been any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, medical treatment or procedure whether or not considered related to the medicinal product. An SAE was defined an any untoward medical occurrence that at any dosage resulted in one or more of the following: death, A life-threatening adverse event (real risk of dying), inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly, required intervention to prevent permanent impairment of damage. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shailender Bhatia | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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Participants were enrolled at 1 investigative site in the United States from 03 January 2012 to 10 April 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A: Tavo-EP | Patients in Cohort A received one cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, after which they proceeded to definitive treatment (surgery and/or radiation therapy) which started between 2 and 4 weeks after the first injection. |
| FG001 | Cohort B: Tavo-EP | Patients in Cohort B received up to 4 cycles (3 daily treatments on Days 1, 5, and 8, per cycle) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, with 12 weeks planned between each cycle, lasting up to 12 months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Analysis Set, all patients who received any amount of the study drug (tavo).
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A: Tavo-EP | Patients in Cohort A received one cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, after which they proceeded to definitive treatment (surgery and/or radiation therapy) which started between 2 and 4 weeks after the first injection. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Who Experienced At Least 2-Fold Increase in Expression of IL-12 Protein in the Tumor Tissue After Intratumoral (IT) pIL-12 Injections and In Vivo Electroporation | The MAGPIX assay was used to assess differential expression of hIL-12 in patient tumor tissue before and after treatment with intratumoral (IT) tavo injections and in vivo electroporation (EP). Expression of hIL-12 was used to identify patients who met the primary endpoint of a 2-fold or higher increase in expression of hIL-12 in tumors after treatment. Fold change was taken as a comparison of hIL-12 expression at Week 3:pre-treatment, Week 6:pre-treatment, Week 8:pre-treatment, or Week 13:pre-treatment over baseline (pre- treatment). The fold change was calculated as log2 (time point/baseline). | Efficacy Analysis Set, all patients from Cohort B who received any amount of the study drug (tavo). | Posted | Number | percentage of participants | Pre-treatment up to Week 13 |
|
From signing of informed consent to 8 weeks after the last dose of study treatment (up to 15 months).
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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 | Cohort A: Tavo-EP | Patients in Cohort A received one cycle (3 daily treatments on Days 1, 5, and 8) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, after which they proceeded to definitive treatment (surgery and/or radiation therapy) which started between 2 and 4 weeks after the first injection. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sharron E Gargosky, Chief Clinical Regulatory Officer | OncoSec Medical Incorporated | +1 858-255-4729 | ClinicalTrialsInfo@OncoSec.com |
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| ID | Term |
|---|---|
| D015266 | Carcinoma, Merkel Cell |
| ID | Term |
|---|---|
| D027601 | Polyomavirus Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| OncoSec Medical System (OMS) | Device | Electroporation via OMS was performed immediately following intratumoral injection of tavo. A sterile applicator containing 6 stainless steel electrodes arranged in a circle were placed around the tumor. The applicator was connected to the OMS power supply and six pulses were administered to each tumor lesion at the approximate point of tavo injection. |
|
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| From signing of informed consent to 8 weeks after the last dose of study treatment (up to 15 months) |
| Objective Response Rate (ORR) in Injected and Non-injected (Distant) Lesions | ORR is defined as the percentage of participants with evaluable lesions that achieved a complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. The same method was used to assess response rate for treated lesions and response rate for non-treated lesions. The best response rate for non-treated lesions was based on the number of patients who had at least one non-treated lesion. | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
| Time to Progression (TTP) | TTP is defined as the number of days between the treatment initiation date (Study Day 1) and the earliest date of documented disease progression as defined by RECIST 1.1 or death that is not associated with prior disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
| Overall Survival | Overall survival is defined as the time in days from the date of first study drug administration to the date of death. | From the start of study treatment until death (up to 15 months) |
| Immunologic Effects of IT pIL-12 Injection and In Vivo EP Measured By: Percentage of Participants With a Positive Fold Change (Log2) in IL-12A Messenger Ribonucleic Acid (mRNA) for Patient Pre- and Post IT pIL 12 EP | Nanostring analysis was performed to determine the expression (mRNA) of IL-12. For each study patient, the fold change (log2 transformed) in IL-12A mRNA as measured by Nanostring was determined using the pre-treatment (screening) biopsy as a reference for the post treatment biopsy. A log2 fold change >=1 is a positive result. | Pre-treatment up to Week 13 |
| Local Regression Rate | Local regression rate is defined as the percentage of participants with ≥30% regression (decrease in size) of at least one assessed local (injected) lesion. | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
| Distant Regression Rate | Distant regression rate is defined as the percentage of participants with ≥30% regression (decrease in size) of at least one assessed distant (non-injected) lesion. | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
| BG001 | Cohort B: Tavo-EP | Patients in Cohort B received up to 4 cycles (3 daily treatments on Days 1, 5, and 8, per cycle) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, with 12 weeks planned between each cycle, lasting up to 12 months. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Patients in Cohort B received up to 4 cycles (3 daily treatments on Days 1, 5, and 8, per cycle) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, with 12 weeks planned between each cycle, lasting up to 12 months. |
|
|
| Secondary | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, medical treatment or procedure and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could have, therefore, been any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, medical treatment or procedure whether or not considered related to the medicinal product. An SAE was defined an any untoward medical occurrence that at any dosage resulted in one or more of the following: death, A life-threatening adverse event (real risk of dying), inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly, required intervention to prevent permanent impairment of damage. | Safety Analysis Set, all patients who received any amount of the study drug (tavo). | Posted | Number | percentage of participants | From signing of informed consent to 8 weeks after the last dose of study treatment (up to 15 months) |
|
|
|
| Secondary | Objective Response Rate (ORR) in Injected and Non-injected (Distant) Lesions | ORR is defined as the percentage of participants with evaluable lesions that achieved a complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. The same method was used to assess response rate for treated lesions and response rate for non-treated lesions. The best response rate for non-treated lesions was based on the number of patients who had at least one non-treated lesion. | Efficacy Analysis Set, all patients from Cohort B who received any amount of the study drug (tavo) and had evaluable lesions. | Posted | Number | percentage of participants | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
|
|
|
| Secondary | Time to Progression (TTP) | TTP is defined as the number of days between the treatment initiation date (Study Day 1) and the earliest date of documented disease progression as defined by RECIST 1.1 or death that is not associated with prior disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Efficacy Analysis Set, all patients from Cohort B who received any amount of the study drug (tavo) and had document disease progression. | Posted | Median | 95% Confidence Interval | days | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
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|
|
| Secondary | Overall Survival | Overall survival is defined as the time in days from the date of first study drug administration to the date of death. | Efficacy Analysis Set, all patients who received any amount of the study drug (tavo). Zero participants were analyzed for overall survival because all patients were alive at their study completion visit. | Posted | From the start of study treatment until death (up to 15 months) |
|
|
| Secondary | Immunologic Effects of IT pIL-12 Injection and In Vivo EP Measured By: Percentage of Participants With a Positive Fold Change (Log2) in IL-12A Messenger Ribonucleic Acid (mRNA) for Patient Pre- and Post IT pIL 12 EP | Nanostring analysis was performed to determine the expression (mRNA) of IL-12. For each study patient, the fold change (log2 transformed) in IL-12A mRNA as measured by Nanostring was determined using the pre-treatment (screening) biopsy as a reference for the post treatment biopsy. A log2 fold change >=1 is a positive result. | Efficacy Analysis Set, all patients from Cohort B who received any amount of the study drug (tavo) and had evaluable lesions. | Posted | Number | percentage of participants | Pre-treatment up to Week 13 |
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|
|
| Secondary | Local Regression Rate | Local regression rate is defined as the percentage of participants with ≥30% regression (decrease in size) of at least one assessed local (injected) lesion. | All patients from Cohorts A and B with evaluable lesions. | Posted | Number | percentage of participants | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
|
|
|
| Secondary | Distant Regression Rate | Distant regression rate is defined as the percentage of participants with ≥30% regression (decrease in size) of at least one assessed distant (non-injected) lesion. | All patients from Cohorts A and B with evaluable lesions. | Posted | Number | percentage of participants | 3-4 weeks after the first dose in each cycle and then every 3 months until disease progression, death or withdrawal of consent (up to 15 months) |
|
|
|
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Cohort B: Tavo-EP | Patients in Cohort B received up to 4 cycles (3 daily treatments on Days 1, 5, and 8, per cycle) of intra-tumoral injection(s) of tavo at a fixed dose of 0.5 mg/mL (up to 4 tumor sites) followed immediately by in vivo electroporation, with 12 weeks planned between each cycle, lasting up to 12 months. | 1 | 12 | 12 | 12 |
| Contusion | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Seroma | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Injection site inflammation | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Injection site discolouration | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (19.0) | Systematic Assessment |
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| Injection site bruising | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Injection site haematoma | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Injection site necrosis | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (19.0) | Systematic Assessment |
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| Injection site cellulitis | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Hepatocellular carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Systematic Assessment |
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| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (19.0) | Systematic Assessment |
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| Lymph node pain | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
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| Diplopia | Eye disorders | MedDRA (19.0) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
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| Lymphoedema | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
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| D014412 |
| Tumor Virus Infections |
| D018278 | Carcinoma, Neuroendocrine |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
|