Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A Phase 2 Study with Safety Lead-in, Evaluating TAS-102 Plus Nivolumab in Participants with Microsatellite Stable Refractory Metastatic Colorectal Cancer
This is a multicenter, single arm, safety lead-in, Phase 2 study, using Simon's 2 stage design evaluating the safety and efficacy of TAS-102 plus nivolumab in participants with Microsatellite-stable refractory metastatic colorectal cancer
Stage 1: Participants will be enrolled and after Cycle 1 treatment, they will be evaluated for the safety and tolerability of the combination therapy. Assuming a tolerated dose is confirmed additional participants evaluable for response will be enrolled and followed for a minimum of 6 months and there will be an interim analysis to assess the safety and efficacy to determine whether the second stage will open for enrollment.
Stage 2: Additional participant evaluable for response assessment will be enrolled and followed for a minimum of 6 months.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAS-102 + Nivolumab | Experimental | Participants received a dose of 35 milligrams per meter square (mg/m^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAS-102 | Drug | One Arm Only (of TAS 102 plus nivolumab) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Immune-Related Overall Response Rate (irORR) | irORR was defined as the percentage of participants achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions)., Partial Response (irPR) was defined as a decrease in the sum of the products of the two largest perpendicular diameters (SPD) by 50 percent (%) or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) was defined as the failure to meet criteria for irCR or irPR in absence of progressive disease (irPD), irPD was defined as at least 25% increase in SPD relative to nadir. | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | DLT: defined as occurrence of any of the following- Hematological toxicities:
Non-hematological toxicities:
Drug-related toxicities:
|
Not provided
Inclusion Criteria:
Exclusion Criteria:
Has a serious illness or medical condition.
Treatment with any of the following within the specified time frame before enrollment:
Previous treatment with TAS-102.
Prior treatment with anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death ligand (anti-PD-L1), anti programmed cell death ligand 2, anti-CD137, anti-OX-40, anti CD40, anti cytotoxic T lymphocyte associated antigen-4 antibodies, or any other immune checkpoint inhibitors.
Unresolved toxicity of >=Common Terminology Criteria for Adverse Events version (CTCAE) version 4.03 grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity).
Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune mediated nephritis and renal dysfunction, immune mediated rash, immune mediated encephalitis, and history of infusion reactions to nivolumab.
Known or assumed hypersensitivity to TAS-102 or nivolumab or any of its ingredients, including polysorbate 80-containing infusion.
Previous severe hypersensitivity reaction to treatment with another mAb.
Pregnant or lactating female.
Inappropriate for entry into this study in the judgment of the investigator.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarah Cannon Research Institute at HealthONE | Denver | Colorado | 80218 | United States | ||
| Florida Cancer Specialists |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33544407 | Derived | Patel MR, Falchook GS, Hamada K, Makris L, Bendell JC. A phase 2 trial of trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable metastatic colorectal cancer. Cancer Med. 2021 Feb;10(4):1183-1190. doi: 10.1002/cam4.3630. Epub 2021 Feb 5. |
Not provided
Not provided
Study results using compiled efficacy and safety data will be published at congress or to a journal, without any identification of the patients.
Not provided
Not provided
Not provided
Not provided
A total of 22 participants were screened out of which 18 participants passed the screening and were enrolled in the study. This study was planned to have 2 stages but only stage1 was completed. The study was halted following an interim analysis and no participants were enrolled in stage 2. Therefore, the data represented is for stage 1 only.
The study was conducted at 3 centers in United States.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | TAS-102 + Nivolumab | Participants received a dose of 35 milligrams per meter square (mg/m^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline population included all enrolled participants who received at least 1 dose of study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | TAS-102 + Nivolumab | Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle). |
| 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 | Immune-Related Overall Response Rate (irORR) | irORR was defined as the percentage of participants achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions)., Partial Response (irPR) was defined as a decrease in the sum of the products of the two largest perpendicular diameters (SPD) by 50 percent (%) or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) was defined as the failure to meet criteria for irCR or irPR in absence of progressive disease (irPD), irPD was defined as at least 25% increase in SPD relative to nadir. | Efficacy population included all participants in the safety population (all participants who received at least 1 dose of study drug) who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up. | Posted | Number | percentage of participants | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
|
From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TAS-102 + Nivolumab | Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
After interim analysis, per study design plan, the trial was stopped for futility before enrollment into Stage 2.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Taiho | Taiho Oncology, Inc. | 844-878-2446 | medicalinformation@taihooncology.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 14, 2016 | Jul 2, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 31, 2017 | Jul 2, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| ID | Term |
|---|---|
| C000613803 | trifluridine tipiracil drug combination |
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| nivolumab | Drug | One Arm Only (of TAS 102 plus nivolumab) |
|
|
| Cycle 1 (each cycle is of 4 weeks) |
| Recommended Phase 2 Dose (RP2D) | RP2D of TAS-102 was evaluated based on the safety and tolerability of the combination therapy of TAS-102 and Nivolumab. | Cycle 1 (each cycle is of 4 weeks) |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs: AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
| Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities | Hematological and chemistry laboratory tests abnormalities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE). | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
| Overall Response Rate (ORR) | ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version 1.1.CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<)10 millimeters (mm). PR was defined as at least a 30 % decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
| Progression-Free Survival (PFS) Based on Immune Related Response-Criteria (irRC) | Immune-related progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on irRC) or death due to any cause. Participants who were alive with no disease progression at the moment of the analysis cut-off date was censored at the date of the last tumor assessment. Per irRC criteria disease progression defined as at least 25% increase in SPD relative to nadir. Analysis was performed using Kaplan-Meier estimates. | From the first dose of study treatment to disease progression or death (up to 53 weeks) |
| Progression-Free Survival (PFS) Based on RECIST Criteria | Progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on RECIST 1.1) or death due to any cause. Per RECIST criteria disease progression defined as least 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study, including the baseline sum. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Definitive new lesion presence also indicated progression. | From the first dose of study treatment to disease progression or death (up to 53 weeks) |
| Disease Control Rate (DCR) Based on irRC Criteria | DCR was defined as the percentage of participants with objective evidence of radiologic complete response (CR), partial response (PR), or stable disease (SD) and was based on the overall best response from each participant as determined from investigator response assessments and following irRC criteria. Per irRC criteria, CR was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions). PR was defined as a decrease in the sum of the products of the two largest perpendicular diameters by 50% or greater by a consecutive assessment at least 4 weeks after first documentation. SD was defined as the failure to meet criteria for irCR or irPR in absence of in absence of irPD. | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
| Disease Control Rate (DCR) Based on RECIST Criteria | DCR was defined as the percentage of participants with objective evidence of radiologic CR, PR, or SD and was based on the overall best response from each participant as determined from investigator response assessments and following RECIST Criteria version 1.1. Per RECIST Criteria CR defined as disappearance of all target lesions. Reduction in any pathological lymph nodes in short axis to <10 mm. PR defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum diameters during study. | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
| Overall Survival (OS) | OS was defined as the time from the first dose of the study treatment to the death in the safety population. Participants alive at the time of the study discontinuation were censored. Analysis was performed using Kaplan-Meier estimates. | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
| Sarasota |
| Florida |
| 34232 |
| United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | TAS-102 + Nivolumab | Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle). |
|
|
| Secondary | Number of Participants With Dose Limiting Toxicities (DLTs) | DLT: defined as occurrence of any of the following- Hematological toxicities:
Non-hematological toxicities:
Drug-related toxicities:
| DLT Evaluable (DLTE) population included all participants in the safety population in Stage 1, prior to confirming the recommended dose, who completed at least 1 cycle (28 days) of study treatment with at least 80% of the study treatment administered, unless the treatment was interrupted because of a DLT. | Posted | Count of Participants | Participants | Cycle 1 (each cycle is of 4 weeks) |
|
|
|
| Secondary | Recommended Phase 2 Dose (RP2D) | RP2D of TAS-102 was evaluated based on the safety and tolerability of the combination therapy of TAS-102 and Nivolumab. | DLTE population included all participants in the safety population in Stage 1, prior to confirming the recommended dose, who completed at least 1 cycle (4 weeks) of study treatment with at least 80% of the study treatment administered, unless the treatment was interrupted because of a DLT. | Posted | Number | mg/m^2 | Cycle 1 (each cycle is of 4 weeks) |
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs: AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. | Safety population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
|
|
|
| Secondary | Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities | Hematological and chemistry laboratory tests abnormalities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE). | Safety population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
|
|
|
| Secondary | Overall Response Rate (ORR) | ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version 1.1.CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<)10 millimeters (mm). PR was defined as at least a 30 % decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. | Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up. | Posted | Number | percentage of participants | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
|
|
|
| Secondary | Progression-Free Survival (PFS) Based on Immune Related Response-Criteria (irRC) | Immune-related progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on irRC) or death due to any cause. Participants who were alive with no disease progression at the moment of the analysis cut-off date was censored at the date of the last tumor assessment. Per irRC criteria disease progression defined as at least 25% increase in SPD relative to nadir. Analysis was performed using Kaplan-Meier estimates. | Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up. | Posted | Median | 95% Confidence Interval | months | From the first dose of study treatment to disease progression or death (up to 53 weeks) |
|
|
|
| Secondary | Progression-Free Survival (PFS) Based on RECIST Criteria | Progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on RECIST 1.1) or death due to any cause. Per RECIST criteria disease progression defined as least 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study, including the baseline sum. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Definitive new lesion presence also indicated progression. | Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up. | Posted | Median | 95% Confidence Interval | months | From the first dose of study treatment to disease progression or death (up to 53 weeks) |
|
|
|
| Secondary | Disease Control Rate (DCR) Based on irRC Criteria | DCR was defined as the percentage of participants with objective evidence of radiologic complete response (CR), partial response (PR), or stable disease (SD) and was based on the overall best response from each participant as determined from investigator response assessments and following irRC criteria. Per irRC criteria, CR was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions). PR was defined as a decrease in the sum of the products of the two largest perpendicular diameters by 50% or greater by a consecutive assessment at least 4 weeks after first documentation. SD was defined as the failure to meet criteria for irCR or irPR in absence of in absence of irPD. | Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up. | Posted | Number | 95% Confidence Interval | percentage of participants | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
|
|
|
| Secondary | Disease Control Rate (DCR) Based on RECIST Criteria | DCR was defined as the percentage of participants with objective evidence of radiologic CR, PR, or SD and was based on the overall best response from each participant as determined from investigator response assessments and following RECIST Criteria version 1.1. Per RECIST Criteria CR defined as disappearance of all target lesions. Reduction in any pathological lymph nodes in short axis to <10 mm. PR defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum diameters during study. | Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up. | Posted | Number | 95% Confidence Interval | percentage of participants | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
|
|
|
| Secondary | Overall Survival (OS) | OS was defined as the time from the first dose of the study treatment to the death in the safety population. Participants alive at the time of the study discontinuation were censored. Analysis was performed using Kaplan-Meier estimates. | Safety population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed is 0 because data were not collected for the outcome measure at particular time point. | Posted | From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks) |
|
|
| 0 |
| 18 |
| 6 |
| 18 |
| 18 |
| 18 |
| Colitis | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
|
| Obstructive uropathy | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 18.1 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Medication error | Injury, poisoning and procedural complications | MedDRA 18.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 18.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 18.1 | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA 18.1 | Systematic Assessment |
|
| Vulvovaginal pain | Reproductive system and breast disorders | MedDRA 18.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rash follicular | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 18.1 | Systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Title | Measurements |
|---|---|
|
| Grade 4: Lymphopenia (lymphocytes low) |
|
| Grade 4: Thrombocytopenia (platelets low) |
|
| Grade 4: Bilirubin High |
|
| Grade 4: Glucose High |
|
| Grade 4: Sodium Low |
|
| Grade 3: Neutropenia (neutrophils low) |
|
| Grade 3: Anemia (hemoglobin low) |
|
| Grade 3: Leukopenia (leukocytes low) |
|
| Grade 3: Lymphopenia (lymphocytes low) |
|
| Grade 3: Thrombocytopenia (platelets low) |
|
| Grade 3: Bilirubin High |
|
| Grade 3: Glucose High |
|
| Grade 3: Sodium Low |
|