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| ID | Type | Description | Link |
|---|---|---|---|
| 1310014396 | Other Identifier | Weill Cornell Medical College IRB |
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| Name | Class |
|---|---|
| Vital Systems Inc. | OTHER |
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This is a clinical research study of an investigational (FDA IND-BB 10091) treatment for patients with advanced colorectal cancer that no longer responds to standard therapies.
The treatment is being evaluated for its effect on tumor growth. It consists of the placement (implantation) of small beads that contain mouse renal adenocarcinoma cells (RENCA macrobeads). The cells in the macrobeads produce substances that have been shown to slow or stop the growth of tumors in experimental animals and veterinary patients. It has been tested in 31 human subjects with different types of cancers in a Phase I safety trial. Phase II studies in patients with colorectal, pancreatic or prostate cancers are in progress
This is a Phase IIb, multicenter, nonrandomized, open-label study with RENCA macrobeads in patients with treatment-resistant, metastatic colorectal carcinoma to determine the effect of RENCA macrobead implantation on overall survival compared with best supportive care.
Two treatment groups will be enrolled in this study, as follows:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Macrobead Implantation Arm | Experimental | patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at an amount of 8 RENCA macrobeads per kilogram of body weight |
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| Best Supportive Care Arm | No Intervention | patients who will receive, or continue receiving, best supportive care, defined as management of symptoms aimed at maintaining or improving quality of life, but not including approved therapies targeting the patient's malignancy |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RENCA macrobeads | Biological |
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| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | The primary objective of this study was to evaluate the efficacy of RENCA macrobead implantation as assessed by overall survival in subjects with treatment-resistant mCRC. | From date of the most recent scan prior to the first macrobead implantation; assessed up to 32 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Performance Status (ECOG Score) | The Eastern Cooperative Oncology Group (ECOG) performance scale is a 5-point scale, where 0 denotes perfect health and 5 is death. It is used by clinicians to assess disease progression and how the disease is affecting the daily living abilities of the patient. The ECOG Performance Status scores are defined as follows:
|
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Marker Response (CEA and CA 19-9) | Tumor markers included serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), and were assessed on all participants in the RENCA macrobead implantation arm at baseline and at subsequent evaluation points to further assess tumor response to RENCA macrobead implantation. A tumor marker response was defined as a greater than or equal to 20% decrease in one or both of CEA or CA 19-9. |
Inclusion Criteria:
Patients in both treatment groups must meet all of the following criteria to be considered eligible to participate in the study:
Patients in Group A must also meet all of the following additional criteria:
ECOG performance status score of 0, 1, or 2.
Adequate hematologic function, defined as follows:
Adequate hepatic function, defined as follows:
Adequate renal function, defined as creatinine ≤2.0 mg/dL.
Adequate coagulation function, defined as follows:
Clinically significant toxic effects of chemotherapy (excluding alopecia), radiotherapy, hormonal therapy, or prior surgery must have resolved to Grade 1 or better, with the exception of peripheral neuropathy, which must have resolved to Grade 2 or better.
Female participants of childbearing potential must have had a negative serum pregnancy test at screening; and must also agree to contraceptive use while on study if sexually active. Male subjects and their partners must have agreed to use condoms.
Exclusion Criteria:
Patients in either treatment group who meet any of the following criteria will be excluded from participating in the study:
Patients in Group A who meet any of the following criteria will be excluded from participating in the study:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas J Fahey, III., M.D. | Weill Cornell Medical Center / New York-Presbyterian Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas Cancer Center | Westwood | Kansas | 66205 | United States | ||
| Weill Cornell Medical Center / The Rogosin Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21266362 | Background | Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, North AJ, Couto CG, Post GS, Waters DJ, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Hydrophilic agarose macrobead cultures select for outgrowth of carcinoma cell populations that can restrict tumor growth. Cancer Res. 2011 Feb 1;71(3):725-35. doi: 10.1158/0008-5472.CAN-10-2258. Epub 2011 Jan 24. | |
| 21266363 |
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70 participants provided informed consent to participate in the study (Group A n=67; Group B n=3). Of these, 41 mCRC patients were enrolled in the RENCA macrobead implantation arm (Group A) and 3 subjects were enrolled in the Best Supportive Care arm (Group B). The 25 subjects who were not enrolled into Group A, after providing informed consent, had failed the respective eligibility criteria.
Participants were recruited based on physician referral at five academic medical centers between March 2013 and November 2017. The first participant was implanted on April 11, 2014 and the last implant was March 7, 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Macrobead Implantation Arm | mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight. RENCA macrobeads |
| FG001 | Best Supportive Care Arm | mCRC patients who had previously decided (independently of this study) to receive, or continue receiving, best supportive care, defined as management of symptoms aimed at maintaining or improving quality of life, but not including approved therapies targeting the patient's malignancy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The analysis population was limited to those in Group A, Macrobead Implantation Arm. Group B, Best Supportive Care, was only able to enroll 3 of 80 participants planned. Per Group B investigators, the entry criteria were flagged as being impossible for reliable enrollment. Therefore, the reported study results are only from participants who were enrolled and implanted with RENCA macrobeads.
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| ID | Title | Description |
|---|---|---|
| BG000 | Macrobead Implantation Arm | mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight. |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Overall Survival | The primary objective of this study was to evaluate the efficacy of RENCA macrobead implantation as assessed by overall survival in subjects with treatment-resistant mCRC. | The analysis population was limited to those in Group A, Macrobead Implantation Arm. Group B, Best Supportive Care, was only able to enroll 3 of 80 participants planned. Per Group B investigators, the entry criteria were flagged as being impossible for reliable enrollment. Therefore, these results focus on the participants who were enrolled and implanted with RENCA macrobeads. | Posted | Median | 95% Confidence Interval | months | From date of the most recent scan prior to the first macrobead implantation; assessed up to 32 months. |
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From date of first macrobead implantation; assessed up to 32 months.
The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs > Grade 2, laboratory values of special interest and all subject deaths.
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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 | Macrobead Implantation Arm | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. The arm reported here includes all patients who had at least one implantation of RENCA macrobeads. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.1) | Systematic Assessment |
Group B was only able to enroll 3/80 participants planned for the best supportive care management arm of this study. As per Group B investigators, the entry criteria were flagged as being impossible for reliable enrollment. Therefore, the results reported here focus on the Group A participants, those which were implanted with RENCA macrobeads.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Betty-Jane Sloan, Clinical Research Manager | The Rogosin Institute | 646-317-0701 | bjsloan@nyp.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 25, 2019 | Dec 3, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Dec 23, 2013 | Dec 4, 2020 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D009369 | Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Activities of Daily Living (KPS Score) | Karnofsky Performance Status (KPS) is a self-rated scale that measures the participant's ability to perform daily functions, ranging from 0 ("dead") to 100 ("normal, no complaints, no evidence of disease). Karnofsky scores are defined as follows:
| Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Global Health Status | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales, three symptom scales, a global health status score, and six single items. The Global Health Status is assessed from 2 of the 30 questions (Question 29 and 30), whose response score ranges on a 7 point scale. The score for physical function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor) and the maximum value is 100 (best outcome, excellent). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Physical Function | TThe European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including physical function), three symptom scales, a global health status score, and six single items. Physical Function is assessed from 5 of the 30 questions (Questions 1-5), whose response score ranges on a 4 point scale. The score for physical function is calculated based on the average score from these 5 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Role Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including role function), three symptom scales, a global health status score, and six single items. Role Function is assessed from 2 of the 30 questions (Questions 6 and 7), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Emotional Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including emotional function), three symptom scales, a global health status score, and six single items. Emotional Function is assessed from 4 of the 30 questions (Questions 21-24), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 4 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Cognitive Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including cognitive function), three symptom scales, a global health status score, and six single items. Cognitive Function is assessed from 2 of the 30 questions (Question 20 and 25), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Social Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including social function), three symptom scales, a global health status score, and six single items. Social Function is assessed from 2 of the 30 questions (Question 26 and 27), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Pain Assessment | Participants were asked to rate their pain on a discrete scale (from 0 = "no pain" to 100 "worst pain imaginable, unbearable"). The worst pain at each time point was used in the analysis. | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
| Change from baseline up to and including day 90 post-Implant 1. |
| Overall Survival by Tumor Marker Response | Overall survival (OS) of participants by tumor marker response. A responder is a participant having a decrease from baseline of 20% or more in CEA or CA 19-9 within 90 days of Implant. OS is the time interval between the date of radiographically documented disease progression and the date of death due to any cause. Participants still alive at the end of the study are censored at 22OCT2018. | 30 months |
| Necrosis Comparison of Tumors Using PET-CT Scan | Tumors were assessed by positron emission tomography (PET)-CT scan at baseline and day 90 following the first RENCA macrobead implantation. The use of [13]F-fluorodeoxyglucose (FDG) uptake for the detection of lesions >1 cm in diameter allowed evaluation of metabolic activity. Decreases in FDG uptake were indicative of metabolic suppression of the tumor. The use of PET-CT scanning indicated anatomical localization, approximate size/volume of primary tumor and metastatic lesion(s), and assessment of metabolic activity of the tumor (as an indicator of metabolic health and necrosis). Disease state is reported as a function of Tumor measurement divided by SUVmax. Changes were assessed between day 90 post RENCA macrobead implant and baseline values. Patients with no change = stable; patients with decreased values = decreased/necrosis, and patients with increased values = increased. | Day 90 post-Implant 1 |
| New York |
| New York |
| 10021 |
| United States |
| Calvary Hospital | The Bronx | New York | 10461 | United States |
| The Ohio State University; OSU Comprehensive Cancer Center | Columbus | Ohio | 43210-1228 | United States |
| Background |
| Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Three-dimensional culture of mouse renal carcinoma cells in agarose macrobeads selects for a subpopulation of cells with cancer stem cell or cancer progenitor properties. Cancer Res. 2011 Feb 1;71(3):716-24. doi: 10.1158/0008-5472.CAN-10-2254. Epub 2011 Jan 24. |
| 24025409 | Background | Gazda LS, Martis PC, Laramore MA, Bautista MA, Dudley A, Vinerean HV, Smith BH. Treatment of agarose-agarose RENCA macrobeads with docetaxel selects for OCT4(+) cells with tumor-initiating capability. Cancer Biol Ther. 2013 Dec;14(12):1147-57. doi: 10.4161/cbt.26455. Epub 2013 Sep 12. |
| 27499645 | Background | Smith BH, Parikh T, Andrada ZP, Fahey TJ, Berman N, Wiles M, Nazarian A, Thomas J, Arreglado A, Akahoho E, Wolf DJ, Levine DM, Parker TS, Gazda LS, Ocean AJ. First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors. Cancer Growth Metastasis. 2016 Aug 2;9:9-20. doi: 10.4137/CGM.S39442. eCollection 2016. |
| 29545721 | Background | Smith BH, Gazda LS, Fahey TJ, Nazarian A, Laramore MA, Martis P, Andrada ZP, Thomas J, Parikh T, Sureshbabu S, Berman N, Ocean AJ, Hall RD, Wolf DJ. Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer: Evaluation of a biological-systems approach to cancer therapy (U.S. FDA IND-BB 10091; NCT 02046174, NCT 01053013). Chin J Cancer Res. 2018 Feb;30(1):72-83. doi: 10.21147/j.issn.1000-9604.2018.01.08. |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Secondary | Performance Status (ECOG Score) | The Eastern Cooperative Oncology Group (ECOG) performance scale is a 5-point scale, where 0 denotes perfect health and 5 is death. It is used by clinicians to assess disease progression and how the disease is affecting the daily living abilities of the patient. The ECOG Performance Status scores are defined as follows:
| Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (day 0 to day 60): Participants who received at least one RENCA macrobead implantation; Implant 2 (day 0 to day 60): Participants who received at least two RENCA macrobead implantations. | Posted | Count of Participants | Participants | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Activities of Daily Living (KPS Score) | Karnofsky Performance Status (KPS) is a self-rated scale that measures the participant's ability to perform daily functions, ranging from 0 ("dead") to 100 ("normal, no complaints, no evidence of disease). Karnofsky scores are defined as follows:
| Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Global Health Status | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales, three symptom scales, a global health status score, and six single items. The Global Health Status is assessed from 2 of the 30 questions (Question 29 and 30), whose response score ranges on a 7 point scale. The score for physical function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor) and the maximum value is 100 (best outcome, excellent). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Physical Function | TThe European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including physical function), three symptom scales, a global health status score, and six single items. Physical Function is assessed from 5 of the 30 questions (Questions 1-5), whose response score ranges on a 4 point scale. The score for physical function is calculated based on the average score from these 5 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Role Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including role function), three symptom scales, a global health status score, and six single items. Role Function is assessed from 2 of the 30 questions (Questions 6 and 7), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Emotional Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including emotional function), three symptom scales, a global health status score, and six single items. Emotional Function is assessed from 4 of the 30 questions (Questions 21-24), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 4 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Cognitive Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including cognitive function), three symptom scales, a global health status score, and six single items. Cognitive Function is assessed from 2 of the 30 questions (Question 20 and 25), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Social Function | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including social function), three symptom scales, a global health status score, and six single items. Social Function is assessed from 2 of the 30 questions (Question 26 and 27), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome. | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Secondary | Pain Assessment | Participants were asked to rate their pain on a discrete scale (from 0 = "no pain" to 100 "worst pain imaginable, unbearable"). The worst pain at each time point was used in the analysis. | Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations. | Posted | Mean | Standard Deviation | score on a scale | Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2 |
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| Other Pre-specified | Tumor Marker Response (CEA and CA 19-9) | Tumor markers included serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), and were assessed on all participants in the RENCA macrobead implantation arm at baseline and at subsequent evaluation points to further assess tumor response to RENCA macrobead implantation. A tumor marker response was defined as a greater than or equal to 20% decrease in one or both of CEA or CA 19-9. | Participants receiving at least one RENCA macrobead implantation whose tumor marker response was greater than or equal to 20% decrease in one or both of CEA or CA 19-9. | Posted | Count of Participants | Participants | Change from baseline up to and including day 90 post-Implant 1. |
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| Other Pre-specified | Overall Survival by Tumor Marker Response | Overall survival (OS) of participants by tumor marker response. A responder is a participant having a decrease from baseline of 20% or more in CEA or CA 19-9 within 90 days of Implant. OS is the time interval between the date of radiographically documented disease progression and the date of death due to any cause. Participants still alive at the end of the study are censored at 22OCT2018. | All participants who had received at least one implantation of RENCA macrobeads. | Posted | Median | 95% Confidence Interval | months | 30 months |
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| Other Pre-specified | Necrosis Comparison of Tumors Using PET-CT Scan | Tumors were assessed by positron emission tomography (PET)-CT scan at baseline and day 90 following the first RENCA macrobead implantation. The use of [13]F-fluorodeoxyglucose (FDG) uptake for the detection of lesions >1 cm in diameter allowed evaluation of metabolic activity. Decreases in FDG uptake were indicative of metabolic suppression of the tumor. The use of PET-CT scanning indicated anatomical localization, approximate size/volume of primary tumor and metastatic lesion(s), and assessment of metabolic activity of the tumor (as an indicator of metabolic health and necrosis). Disease state is reported as a function of Tumor measurement divided by SUVmax. Changes were assessed between day 90 post RENCA macrobead implant and baseline values. Patients with no change = stable; patients with decreased values = decreased/necrosis, and patients with increased values = increased. | Participants who had received at least one macrobead implant and for whom baseline PET-CT scan and day 90 post-Implant 1 PET-CT scan data were available. n= 26 subjects; 77 lesions evaluated | Posted | Count of Units | lesions | Day 90 post-Implant 1 | lesions | lesions |
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|
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| 36 |
| 41 |
| 27 |
| 41 |
| 41 |
| 41 |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (16.1) | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Large intestinal obstruction | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Disease progression | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Pyrexia | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Fatigue | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Malaise | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Pain | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Peritonitis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Abdominal abscess | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Abdominal infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Empyema | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Spinal column injury | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
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| Activated partial thromboplastin time prolonged | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Blood biliriubin increased | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Failure to thrive | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Cerebellar tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.1) | Systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Dysarthria | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Mental status changes | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
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| Renal failure acute | Renal and urinary disorders | MedDRA (16.1) | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal pain, upper | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Proctalgia | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Pyrexia | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Oedema peripheral | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Asthenia | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Chills | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Gait disturbance | General disorders | MedDRA (16.1) | Systematic Assessment | General disorders and administration site conditions |
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| Urinary tract infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
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| Incision site pain | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Activated partial thromboplastin time prolonged | Investigations | MedDRA (16.1) | Systematic Assessment |
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| International normalised ratio increased | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Abdominal pain, lower | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
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| Incision site complication | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
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| Blood alkaline phosphatase, increased | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Blood creatinine, increased | Investigations | MedDRA (16.1) | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Flank Pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
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| Restlessness | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (16.1) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Uticaria | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
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Sponsor retains the first right for scientific disclosure of study results. PI may draft a study results disclosure for scientific publication following the earlier of sponsor's disclosure or 12 months after study completion at all sites. Sponsor has 60 days to review PI's draft for patentable subject matter or confidential information. PI will delete any confidential information and delay any disclosure for another 60 days for sponsor to secure proprietary protection.
| 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 |
| ECOG Score 1 |
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| ECOG Score 2 |
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| ECOG Score 3 |
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| ECOG Score 4 |
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| ECOG Score 5 |
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