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The toxicity seemed to outweigh the benefit.
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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
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The purpose of this study is evaluate the response, safety and tolerability in subjects receiving the investigational drugs, RAD001 and LBH589. Subjects in Part 1 will receive one drug for four cycles followed by 4 cycles of the second drug unless they achieve complete remission. Subjects in a complete remission may receive up to 6 cycles of study drug and will not receive the next study drug until there is evidence of disease progression. Subjects in Part 2 will receive both drugs together for at least 2 cycles and up to 13 if tolerated.
This will be a prospective, non-randomized, un-blinded phase 2 efficacy trial using a mechanistic target of rapamycin (mTOR) inhibitor and a histone deacetylase (HDAC) inhibitor for epigenetic targeted therapies.
Subjects will receive RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be assessed for disease status after 2 cycles and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better les may receive up to 13 cycles. LBH589 was given at 40mg when the study first opened and was changed to 20mg po shortly thereafter. LBH589 is taken on days M/W/F. RAD001 was given at 10mg po daily for Part 1. In Part 2, LBH589 is given at 15mg and RAD001 is given at 7.5mg.
Treatment will be administered on an outpatient basis. Patients will be followed for up to 2 years after completion of therapy or until progression of disease or death.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1a (RAD001 followed by LBH589) | Experimental | Part 1a: Sequential single agent therapy with RAD001 and LBH589. Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. |
|
| Arm 1b (LBH589 followed by RAD001) | Experimental | Part 1b: Sequential single agent therapy with LBH589 and RAD001 . Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. |
|
| Doublet (Combination RAD001 and LBH589) | Experimental | Subjects will receive the doublet of RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be evaluated for the disease status after completion of cycle two and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better may receive up to 13 cycles. LBH589 will start at 15mg po three days a week at least 2 days apart such as on days M/W/F or T/Th/Sat and RAD001 will start at 7.5mg po daily. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RAD001 | Drug | 10 mg/day for Part 1 of the trial |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate | Overall Response Rate is the number of participants with a partial and complete response assessed by the Updated Cheson criteria for lymphoma. A complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy and normalization of those biochemical abnormalities. If a subject has residual lesions on CT scan and the disease was fluorodeoxyglucose (FDG) avid pre-treatment, then that subject will be considered to be in a complete response. Partial response is a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease | after 2 cycles of each study drug or after 2 cycles of doublet, up to 24 weeks |
| Assessment of Association Between Observed Response to RAD001 and LBH589 and the Response Predicted by Molecular Signatures Developed in Our Pre-clinical Model | We will estimate the association of the molecular signature-predicted response to the doublet (CR+PR) with the observed response. All evaluable patients will be used in estimating response. The chi-square test with one-sided alpha of 0.10 will be used to test for the association between predicted and observed responses. Contingency tables will be used to present these associations. | From the start of combination therapy until a maximum of 2 years after completion of therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Summary of Adverse Events (AEs) | Counts of adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose) experienced by patients on study drug(s). National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) is used to assess severity. Relatedness to study drug is assessed by the investigator. | From the time of first dose of study drug until 4 weeks after participant has stopped study drug; up to 1 year |
Not provided
Inclusion Criteria:
de novo or transformed Diffuse large B cell non-Hodgkin lymphoma (DLBCL). DLBCL-like lymphomas allowed:
Refractory or relapsed disease to >/= 1 prior treatment regimen: should include autologous stem cell transplant unless patient refused or ineligible.
Age > 18 years old
Eastern Cooperative Oncology Group (ECOG) performance status <2.
Measurable or evaluable disease by physical exam, radiographs or bone marrow involvement
Frozen tumor or paraffin-embedded sample available.
3-4 core fresh/fresh-frozen biopsy specimens available. Leukapheresis may be done for patients with leukocytosis.
Laboratory Values per protocol.
Exclusion Criteria:
Laboratory Values
Unlimited prior chemotherapy regimens, however:
No prior exposure to RAD001 or LBH589 or drugs that target mTOR (sirolimus, temsirolimus, etc) or HDAC (vorinostat)
No chemotherapy, biologics or immunotherapy < 2 weeks before registration (6 weeks if last received bis-chloroethylnitrosourea (BCNU) or mitomycin C). Subjects must be recovered from therapy-related non-hematological toxicities to < grade 1 or baseline if started with > grade 1 toxicity.
No time limit for radiation prior to registration.
No radioimmunotherapy < 2 months prior to registration. Subjects must be recovered from therapy-related toxicities to < grade 1 or baseline if started with > grade 1 toxicity.
No prior allogeneic stem cell transplantation unless allogeneic engraftment is <2%.
Subjects receiving chronic, systemic treatment with corticosteroids = to >20mg of prednisone per day.
History of other primary malignancy < 3 years ago, except inactive basal, squamous cell carcinoma of the skin or superficial melanoma only requiring excision, prostate cancer with a prostate specific antigen (PSA) stable for >/=3 months, carcinoma in situ of cervix.
Major surgery < 4 weeks before or Minor surgery < 2 weeks before registration. Subjects must be recovered from toxicities to < grade 1 or baseline if started with > grade 1 toxicity.
Investigational drugs < 4 weeks prior to registration.
Impaired Cardiac Function per protocol.
Pregnant or breastfeeding females or adults of reproductive potential not using effective birth control
Diffusing capacity or transfer factor of the lung for carbon monoxide (DLCO) < 40% if tested (per protocol).
Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry.
Immunization with live attenuated vaccines < 1 week of study entry
Impaired GI function or GI disease that may alter absorption of RAD001 or LBH589
Concurrent severe &/or uncontrolled medical conditions
Medications with risk of prolonging QT interval or inducing torsade de pointes or interacting with LBH589 and RAD001 may be used per the protocol.
Active bleeding tendency
Positive for HIV.
Positive for Hepatitis C virus (HCV).
History of non-compliance to medical regimens.
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| Name | Affiliation | Role |
|---|---|---|
| Anne W. Beaven, MD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
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Fifty (50) participants signed consent. Eleven subjects were screen failures. The PI removed three subjects prior to treatment to receive alternate therapy. Three subjects chose to withdraw from the study prior to treatment.
The study opened to enrollment in October, 2009. 50 subjects were consented until enrollment closure in April 2015. Patients were recruited at the Duke Cancer Center Hematology clinic.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1a (RAD001 Followed by LBH589) | Part 1a: Sequential single agent therapy with RAD001 and LBH589. Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
| FG001 | Arm 1b (LBH589 Followed by RAD001) | Part 1b: Sequential single agent therapy with LBH589 and RAD001 . Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
| FG002 | Doublet (Combination RAD001 and LBH589) | Subjects will receive the doublet of RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be evaluated for the disease status after completion of cycle two and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better may receive up to 13 cycles. LBH589 will start at 15mg po three days a week at least 2 days apart such as on days M/W/F or T/Th/Sat and RAD001 will start at 7.5mg po daily. Doublet (RAD001 and LBH589): RAD001 7.5 mg by mouth daily and LBH589 15 mg by mouth on Monday/Wednesday/Friday during Part 2. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1a (RAD001 Followed by LBH589) | Part 1a: Sequential single agent therapy with RAD001 and LBH589. Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Overall Response Rate | Overall Response Rate is the number of participants with a partial and complete response assessed by the Updated Cheson criteria for lymphoma. A complete response is complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy and normalization of those biochemical abnormalities. If a subject has residual lesions on CT scan and the disease was fluorodeoxyglucose (FDG) avid pre-treatment, then that subject will be considered to be in a complete response. Partial response is a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease | Patients have to be on each drug for at least 2 cycles to be evaluable for response. | Posted | Number | participants | after 2 cycles of each study drug or after 2 cycles of doublet, up to 24 weeks |
|
From the time of consent until 4 weeks after the last dose of study drug; approximately 1 year.
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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 | Arm 1a (RAD001 Followed by LBH589) | Part 1a: Sequential single agent therapy with RAD001 and LBH589. Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anne Beaven, MD | Duke University Medical Center | 919-684-8964 | anne.beaven@duke.edu |
Not provided
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068338 | Everolimus |
| D000077767 | Panobinostat |
| ID | Term |
|---|---|
| D020123 | Sirolimus |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D006877 |
Not provided
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Not provided
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|
| LBH589 | Drug | 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
|
|
| Doublet (RAD001 and LBH589) | Drug | RAD001 7.5 mg by mouth daily and LBH589 15 mg by mouth on Monday/Wednesday/Friday during Part 2. |
|
| Distribution of Change Across Time of mTOR and HDAC-I Inhibition From Baseline Until After the 1st 2 Cycles of Study Drug in Patients Who Received LBH and RAD. | Serum markers will be measured on the first day of cycle 1 and on the first day of cycle 3. The distribution of change across time in a marker will be summarized. | after 2 cycles of study therapy; up to 8 weeks |
| Evaluate the Association of Observed Response to the Doublet With the Response Predicted by Molecular Signatures for Activated B Cell Like (ABC) DLBCL and for Germinal Center B Cell Like (GCB) DLBCL. | Response rates seen in subjects with activated B cell like DLBCL and for Germinal center B cell like DLBCL will be reported and assessed to see if GCB is associated with improved outcomes compared to ABC in subjects with relapsed disease who have received RAD + LBH. We will estimate the association of the ABC and GCB with the observed response. All evaluable patients will be used in estimating response. The chi-square test with one-sided alpha of 0.10 will be used to test for the association between predicted and observed responses. The number of responses to treatment were so few that we did not think we could get enough meaningful data for analysis. | up to 13 cycles of therapy; approximately 1 year |
| Adverse Event |
|
| BG001 | Arm 1b (LBH589 Followed by RAD001) | Part 1b: Sequential single agent therapy with LBH589 and RAD001 . Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
| BG002 | Doublet (Combination RAD001 and LBH589) | Subjects will receive the doublet of RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be evaluated for the disease status after completion of cycle two and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better may receive up to 13 cycles. LBH589 will start at 15mg po three days a week at least 2 days apart such as on days M/W/F or T/Th/Sat and RAD001 will start at 7.5mg po daily. Doublet (RAD001 and LBH589): RAD001 7.5 mg by mouth daily and LBH589 15 mg by mouth on Monday/Wednesday/Friday during Part 2. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Arm 1a (RAD001 Followed by LBH589) |
Part 1a: Sequential single agent therapy with RAD001 and LBH589. Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
| OG001 | Arm 1b (LBH589 Followed by RAD001) | Part 1b: Sequential single agent therapy with LBH589 and RAD001 . Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial |
| OG002 | Doublet (Combination RAD001 and LBH589) | Subjects will receive the doublet of RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be evaluated for the disease status after completion of cycle two and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better may receive up to 13 cycles. LBH589 will start at 15mg po three days a week at least 2 days apart such as on days M/W/F or T/Th/Sat and RAD001 will start at 7.5mg po daily. Doublet (RAD001 and LBH589): RAD001 7.5 mg by mouth daily and LBH589 15 mg by mouth on Monday/Wednesday/Friday during Part 2. |
|
|
| Primary | Assessment of Association Between Observed Response to RAD001 and LBH589 and the Response Predicted by Molecular Signatures Developed in Our Pre-clinical Model | We will estimate the association of the molecular signature-predicted response to the doublet (CR+PR) with the observed response. All evaluable patients will be used in estimating response. The chi-square test with one-sided alpha of 0.10 will be used to test for the association between predicted and observed responses. Contingency tables will be used to present these associations. | The number of responses to treatment were so few that we did not think we could get enough meaningful data for analysis. Therefore, molecular analysis was not performed and no results are available. | Posted | From the start of combination therapy until a maximum of 2 years after completion of therapy |
|
|
| Secondary | Summary of Adverse Events (AEs) | Counts of adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose) experienced by patients on study drug(s). National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) is used to assess severity. Relatedness to study drug is assessed by the investigator. | Participants who consented to the study and took study drug were analyzed for this outcome measure. Total number of events per CTCAE v4 category per arm are reported if more than one event occurred. | Posted | Number | events | From the time of first dose of study drug until 4 weeks after participant has stopped study drug; up to 1 year |
|
|
|
| Secondary | Distribution of Change Across Time of mTOR and HDAC-I Inhibition From Baseline Until After the 1st 2 Cycles of Study Drug in Patients Who Received LBH and RAD. | Serum markers will be measured on the first day of cycle 1 and on the first day of cycle 3. The distribution of change across time in a marker will be summarized. | The number of responses to treatment were so few that we did not think we could get enough meaningful data for analysis. Therefore, serum marker analysis was not performed and no results are available. | Posted | after 2 cycles of study therapy; up to 8 weeks |
|
|
| Secondary | Evaluate the Association of Observed Response to the Doublet With the Response Predicted by Molecular Signatures for Activated B Cell Like (ABC) DLBCL and for Germinal Center B Cell Like (GCB) DLBCL. | Response rates seen in subjects with activated B cell like DLBCL and for Germinal center B cell like DLBCL will be reported and assessed to see if GCB is associated with improved outcomes compared to ABC in subjects with relapsed disease who have received RAD + LBH. We will estimate the association of the ABC and GCB with the observed response. All evaluable patients will be used in estimating response. The chi-square test with one-sided alpha of 0.10 will be used to test for the association between predicted and observed responses. The number of responses to treatment were so few that we did not think we could get enough meaningful data for analysis. | The number of responses to treatment were so few that we did not think we could get enough meaningful data for analysis. Therefore, molecular analysis was not performed and no results are available. | Posted | up to 13 cycles of therapy; approximately 1 year |
|
|
| 1 |
| 10 |
| 10 |
| 10 |
| EG001 | Arm 1b (LBH589 Followed by RAD001) | Part 1b: Sequential single agent therapy with LBH589 and RAD001 . Each agent will be given for four-six 28-day cycles. Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period. Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease. There will be a 1-6 week 'washout' period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient's best interest. RAD001: 10 mg/day for Part 1 of the trial LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial | 1 | 5 | 5 | 5 |
| EG002 | Doublet (Combination RAD001 and LBH589) | Subjects will receive the doublet of RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be evaluated for the disease status after completion of cycle two and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better may receive up to 13 cycles. LBH589 will start at 15mg po three days a week at least 2 days apart such as on days M/W/F or T/Th/Sat and RAD001 will start at 7.5mg po daily. Doublet (RAD001 and LBH589): RAD001 7.5 mg by mouth daily and LBH589 15 mg by mouth on Monday/Wednesday/Friday during Part 2. | 6 | 18 | 18 | 18 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Atrial flutter | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Colitis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cognitive disturbance | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Bloating | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Gastrointestinal - Other (Burping) | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Gastrointestinal - Other (Gas) | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Gastroparesis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Mucositis Oral | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Stomach pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Edema face | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Non-cardiac Chest pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Infections and Infestations - Other (cellulitis) | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Cholesterol high | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Weight loss | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Acidosis | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Athralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Agitation | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Depression | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dysphagia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cystitis noninfective | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hematuria | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Genital edema | Reproductive system and breast disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other (Dry Throat) | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Bullous dermatitis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dermatitis radiation | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other (Rash, NOS) | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Flushing | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hot flashes | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D009369 |
| Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D000588 | Amines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
|
| General Disorder AEs |
|
| Investigation (Lab) AEs |
|
| Metabolism and Nutrition AEs |
|
| Musculoskeletal and Connective Tissue AEs |
|
| Nervous System AEs |
|
| Renal and Urinary AEs |
|
| Reproductive System AEs |
|
| Respiratory, thoracic and mediastinal AEs |
|
| Skin and Subcutaneous Tissue AEs |
|
| Vascular AEs |
|