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| Name | Class |
|---|---|
| Celldex Therapeutics | INDUSTRY |
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Based on promising data from our laboratory demonstrating synergy between ablative local radiotherapy and FLT3 ligand immunotherapy in murine NSCLC models, investigators are performing a phase II study combining FLT3L immunotherapy and SBRT for patients with advanced NSCLC that has progressed following standard systemic therapy. All patients will receive daily subcutaneous injections of CDX-301 (75 µg/kg) for 5 days, beginning on the first day of SBRT. SBRT will be delivered to a single pulmonary or extrapulmonary lesion. The SBRT regimen will depend on the size and location of the target lesion. The primary endpoint will be progression-free survival at 4 months, defined using immune-related response criteria (irRC).
Primary Objective
Secondary Objectives
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SBRT + FLT3 Ligand Immunotherapy | Experimental | Patients will be treated with stereotactic body radiotherapy (SBRT) to a single pulmonary or extrapulmonary lesion as well as FLT3 immunotherapy. FLT3 Ligand Therapy (CDX-301)
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FLT3 Ligand Therapy (CDX-301) | Drug | See Arm 1 descriptions |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival | The primary endpoint is progression-free survival rate at four months (PFS4), defined as the rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (~4 months) after initiation of study therapy. | 4 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicities (DLTs) | The number of participants with evidence of DLTs will be tabulated. For the purposes of this study, a DLT will be defined as any grade 3-5 treatment-emergent adverse event toxicity, scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and occurring within 30 days after treatment with SBRT in combination with FLT3 ligand therapy (after the first treatment cycle). Asymptomatic laboratory abnormalities (eg: leukocytosis) that do not require intervention will not be counted as DLTs. For subjects who receive more than one "cycle" of SBRT and FLT3 ligand, only adverse events that occur after the first cycle will be scored as potential DLTs. |
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Inclusion Criteria:
Exclusion Criteria:
Less than 21 days between registration and the last receipt of chemotherapy, biotherapy, immunotherapy, radiotherapy (excluding palliative radiotherapy), or major surgery. Prior receipt of immunomodulatory therapy (eg: nivolumab) is permitted, as long as there has been a 21 day washout period following the most recent treatment.
Untreated central nervous system metastases. Patients with a history of brain metastases must have had no CNS-directed therapy within the past 60 days and radiological assessment within 30 days of study entry demonstrating a lack of progressive CNS disease
Ongoing or recent (within 21 days prior to study entry) use of high dose oral corticosteroids (.2 mg of dexamethasone daily or equivalent). Intranasal and/or inhaled corticosteroid use is permitted.
Any unresolved CTCAE grade >2 toxicity from previous anti-cancer therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study therapy (eg, hearing loss)may be enrolled after discussion with the principal investigators.
History of allogeneic organ transplant or autoimmune disease
Active malignancy, other than NSCLC, for which systemic therapy is indicated. History of adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy asides from hormonal therapy, adequately treated stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for >= 5 years is permitted.
Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by the treating physicians
The following laboratory results, within 10 days of first study drug administration:
Women of child bearing potential: positive pregnancy test (serum)
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| Name | Affiliation | Role |
|---|---|---|
| Nitin Ohri, MD | Albert Einstein College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Montefiore Medical Center | The Bronx | New York | 10467 | United States |
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33 patients signed informed consent however 29 patients were enrolled and randomized into the study.
The recruitment period spanned from July 2016 through 1/23/2020. All patients enrolled into the study were enrolled at Montefiore Medical Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | SBRT + FLT3 Ligand Immunotherapy | Patients will be treated with stereotactic body radiotherapy (SBRT) to a single pulmonary or extrapulmonary lesion as well as FLT3 immunotherapy. FLT3 Ligand Therapy (CDX-301)
FLT3 Ligand Therapy (CDX-301): See Arm 1 descriptions Stereotactic Body Radiotherapy (SBRT): See Arm 1 descriptions |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Baseline characteristics provided for the 29 patients who consented and completed the study. As noted in the participant flow module, 2 other patients screen failed, 1 patient died prior to treatment initiation, and 1 patient was removed from study prior to treatment due to disease progression.
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| ID | Title | Description |
|---|---|---|
| BG000 | SBRT + FLT3 Ligand Immunotherapy | Patients will be treated with stereotactic body radiotherapy (SBRT) to a single pulmonary or extrapulmonary lesion as well as FLT3 immunotherapy. FLT3 Ligand Therapy (CDX-301)
FLT3 Ligand Therapy (CDX-301): See Arm 1 descriptions Stereotactic Body Radiotherapy (SBRT): See Arm 1 descriptions |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | 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 | Progression-Free Survival | The primary endpoint is progression-free survival rate at four months (PFS4), defined as the rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (~4 months) after initiation of study therapy. | Posted | Count of Participants | Participants | 4 Months |
|
Patients were monitored for the onset of Adverse Events for 32 weeks following treatment. Patients were assessed for All-cause Mortality up to 5 years
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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 | SBRT + FLT3 Ligand Immunotherapy | Patients will be treated with stereotactic body radiotherapy (SBRT) to a single pulmonary or extrapulmonary lesion as well as FLT3 immunotherapy. FLT3 Ligand Therapy (CDX-301)
FLT3 Ligand Therapy (CDX-301): See Arm 1 descriptions Stereotactic Body Radiotherapy (SBRT): See Arm 1 descriptions |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Nitin Ohri | Montefiore Medical Center | 718-920-7750 | nitin.ohri@einsteinmed.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 6, 2021 | Feb 26, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| D016634 | Radiosurgery |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
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| Stereotactic Body Radiotherapy (SBRT) |
| Radiation |
See Arm 1 descriptions |
|
|
| 30 days |
| Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) | Radiographic Response will be scored using RECIST V1.1 criteria based on 1st post-treatment imaging to quantify objective measures of change in tumor burden. RECIST uses a max of 10 target lesions per patient to determine when tumors in cancer patients improve, stay the same, or worsen during treatment. RECIST will be used to quantify the percentage of patients demonstrating Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), as follows: CR - resolution of all target lesions to background levels PR - at least 30% decrease in sum of diameters of target lesions (noting baseline diameters) SD - neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD (noting smallest sum on study) PD - at least 20% increase in sum of diameters of target lesions (noting smallest sum on study); absolute increase of 5mm must be demonstrated; >=1 new lesion is considered PD If no CT/PET at a specific timepoint = "Not Evaluable" | Up to 27 months post-randomization |
| Radiographic Response Rate Based on PET Response Criteria in Solid Tumors (PERCIST) | Radiographic Response will be scored using PERCIST criteria based on the first PET imaging done. PERCIST is a set of rules that define when tumors in cancer patients improve, stay the same, or worsen during treatment, based on imaging data. PERCIST criteria will be used to quantify the percentage of patients demonstrating Complete Metabolic Response (CMR), Partial Metabolic Response (PMR), Stable Metabolic Disease (SMD), Progressive Metabolic Disease (PMD), or Not Evaluable (NE) as follows: CMR - complete resolution of 18F-FDG uptake, disappearance of all target lesions to background levels, no new 18F-FDG lesions PMR - reduction of a minimum of 30% in target measurable tumor 18F-FDG SUL peak, no increase >30% in all lesions; no new lesions SMD - no CMR, PMR or PMD; no new lesions PMD - >30% increase in 18F-FDG peak; OR visible increase in extent of tumor uptake; OR new 18F-FDG lesions If CT/PET was not done at a specific timepoint, result will be considered "Not Evaluable" | Up to 27 months post-randomization |
| Overall Survival (OS) | Overall survival (OS) is defined as the percentage of patients alive at 5 years post-randomization. Data of subjects without a death record will be censored on the last known survival date. | From date of treatment to date of death, up to 5 years |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Dose Limiting Toxicities (DLTs) | The number of participants with evidence of DLTs will be tabulated. For the purposes of this study, a DLT will be defined as any grade 3-5 treatment-emergent adverse event toxicity, scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and occurring within 30 days after treatment with SBRT in combination with FLT3 ligand therapy (after the first treatment cycle). Asymptomatic laboratory abnormalities (eg: leukocytosis) that do not require intervention will not be counted as DLTs. For subjects who receive more than one "cycle" of SBRT and FLT3 ligand, only adverse events that occur after the first cycle will be scored as potential DLTs. | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) | Radiographic Response will be scored using RECIST V1.1 criteria based on 1st post-treatment imaging to quantify objective measures of change in tumor burden. RECIST uses a max of 10 target lesions per patient to determine when tumors in cancer patients improve, stay the same, or worsen during treatment. RECIST will be used to quantify the percentage of patients demonstrating Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), as follows: CR - resolution of all target lesions to background levels PR - at least 30% decrease in sum of diameters of target lesions (noting baseline diameters) SD - neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD (noting smallest sum on study) PD - at least 20% increase in sum of diameters of target lesions (noting smallest sum on study); absolute increase of 5mm must be demonstrated; >=1 new lesion is considered PD If no CT/PET at a specific timepoint = "Not Evaluable" | Posted | Count of Participants | Participants | Up to 27 months post-randomization |
|
|
|
| Secondary | Radiographic Response Rate Based on PET Response Criteria in Solid Tumors (PERCIST) | Radiographic Response will be scored using PERCIST criteria based on the first PET imaging done. PERCIST is a set of rules that define when tumors in cancer patients improve, stay the same, or worsen during treatment, based on imaging data. PERCIST criteria will be used to quantify the percentage of patients demonstrating Complete Metabolic Response (CMR), Partial Metabolic Response (PMR), Stable Metabolic Disease (SMD), Progressive Metabolic Disease (PMD), or Not Evaluable (NE) as follows: CMR - complete resolution of 18F-FDG uptake, disappearance of all target lesions to background levels, no new 18F-FDG lesions PMR - reduction of a minimum of 30% in target measurable tumor 18F-FDG SUL peak, no increase >30% in all lesions; no new lesions SMD - no CMR, PMR or PMD; no new lesions PMD - >30% increase in 18F-FDG peak; OR visible increase in extent of tumor uptake; OR new 18F-FDG lesions If CT/PET was not done at a specific timepoint, result will be considered "Not Evaluable" | Posted | Count of Participants | Participants | Up to 27 months post-randomization |
|
|
|
| Secondary | Overall Survival (OS) | Overall survival (OS) is defined as the percentage of patients alive at 5 years post-randomization. Data of subjects without a death record will be censored on the last known survival date. | Posted | Count of Participants | Participants | From date of treatment to date of death, up to 5 years |
|
|
|
| 26 |
| 29 |
| 23 |
| 29 |
| 29 |
| 29 |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Abdominal Pain, Left Upper Quadrant Pain, Epigastric Pain |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Chest Pain | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Sinus Tachycardia | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Sinus Tachycardia, Tachycardia |
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| Productive Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Non-Cardiac Chest Pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | Signification hemoglobin drop to <6 |
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| Leukocytosis | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Sepsis | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
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| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Cardiac Arrest | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Acute Kidney Injury | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Stroke | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Disease Progression | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment | NSCLC |
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| Fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Fatigue, Weakness |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Dyspnea, Shortness of Breath, Dyspnea on Exertion |
|
| Peripheral Sensory Neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Term: Peripheral Neuropathy |
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| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Bullous Dermatitis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Skin Blister, Dermatitis |
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| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Anorexia, Loss of Appetite, Decreased Appetite |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pain in Extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Pain in Extremity; Pain in Lower Extremity |
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| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hypotension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Fever | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pain | General disorders | CTCAE (4.0) | Non-systematic Assessment | Described as 'general' |
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| Skin Hypopigmentation | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Term: Vitiligo/Halo Nevi |
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| Dizziness | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Non-cardiac Chest Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Chest Pain, Flank Pain, Non-cardiac chest pain No documentation of cardiac related-chest pain |
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| Peripheral Sensory Neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Term: Sensory Neuropathy |
|
| Esophagitis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pain - Suprapubic | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Term: Pain Suprapubic Area |
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| Edema Limbs | General disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Edema - lower extremity; Edema bilateral lower extremity to shins; Edema left leg; bilateral leg edema; Edema - left shoulder/armpit |
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| Dysphagia | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Laryngeal Hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Term: Cough with Hemoptysis |
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| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Chills | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Chest Wall Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Chest Wall Discomfort. Left Chest Wall Pain |
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| Abdominal Pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Terms: Abdominal Pain, Left Upper Quadrant Pain, Epigastric Pain |
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| Anxiety | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Injection Site Reaction | General disorders | CTCAE (4.0) | Non-systematic Assessment | At site of FLT3L injection |
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| Dry Eye | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Blurred Vision | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Neck Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Left-sided |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Flu Like Symptoms | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Pelvic Pain | Reproductive system and breast disorders | CTCAE (4.0) | Non-systematic Assessment | Verbatim Term: Pain - left hip/pelvic. Corresponds to an iliac crest metastasis visualized on recent PET/CT scan |
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| Weight Loss | Investigations | CTCAE (4.0) | Non-systematic Assessment |
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| Paresthesia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
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| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D013514 |
| Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| Progressive Disease (PD) |
|
| Not Evaluable (NE) |
|
| Progressive Metabolic Disease (PMD) |
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| Not Evaluable |
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