Phase 2 Study of Sym004 for Adult Patients With Recurrent Glioblastoma
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the activity of Sym004, a recombinant antibody mixture that specifically binds to EGFR, in patients diagnosed with recurrent glioblastoma whose tumor is EGFR amplified. This is a phase 2 study that will accrue patients with WHO grade IV recurrent malignant glioma (glioblastoma or gliosarcoma) in two cohorts to assess the efficacy of Sym004.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The purpose of this study is to assess the activity of Sym004, a recombinant antibody mixture that specifically binds to EGFR, in patients diagnosed with recurrent glioblastoma whose tumor is EGFR amplified. The primary objective is to assess the activity of Sym004 in patients with recurrent glioblastoma that are either non-bevacizumab failures (Cohort 1) or who have previously failed bevacizumab (Cohort 2), in terms of 6-month progression-free survival (PFS6). Secondary objectives include: 1. Determine the safety of Sym004 in recurrent glioblastoma (GBM) patients; 2. Estimate response rate (RR) within the two cohorts of recurrent GBM patients; 3. Describe overall survival (OS) within the two cohorts of recurrent GBM patients; 4. Describe overall median progress free survival (PFS) within the two cohorts of recurrent GBM patients.
This is a phase 2 study that will accrue patients with WHO grade IV recurrent malignant glioma (glioblastoma or gliosarcoma) in two cohorts to assess the efficacy of Sym004. Both cohorts will accrue simultaneously, with 36 subjects in Cohort 1 and 25 subjects in Cohort 2 at a dose of 18 mg/kg Sym004 given intravenously every 2 weeks. A treatment cycle will be 4 weeks.
Twenty-five subjects have been treated at the 18 mg/kg dose of Sym004. Beginning in August 2017, the dose of Sym004 will be increased to 24 mg/kg. Sixty-five additional subjects (36 in Cohort 1 and 29 in Cohort 2) will be treated at the new dose level.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: non-bevacizumab failures - 18 mg/kg Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. |
Drug: Sym004 - 18 mg/kg
Sym004 was dosed at 18 mg/kg intravenously every two weeks.
|
| Experimental: bevacizumab failures - 18 mg/kg Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. |
Drug: Sym004 - 18 mg/kg
Sym004 was dosed at 18 mg/kg intravenously every two weeks.
|
| Experimental: non-bevacizumab failures - 24 mg/kg Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. |
Drug: Sym004 - 24 mg/kg
Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks.
|
| Experimental: bevacizumab failures - 24 mg/kg Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. |
Drug: Sym004 - 24 mg/kg
Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks.
|
Outcome Measures
Primary Outcome Measures
- Six-month Progression-free Survival (PFS6) [6 months]
Within each cohort, the percentage of participants alive and progression-free at 6 months after the start of Sym004 treatment will be determined. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.
Secondary Outcome Measures
- Percentage of Participants Who Experience Grade 3, 4 or 5 Adverse Events [2 years]
Within each cohort, the percentage of participants who experience grade 3, 4 or 5 adverse events that are possibly, probably or definitely related to study treatment will be calculated.
- Radiographic Response [2 years]
Within each cohort, the percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria will be determined. Complete Response (CR) is defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) is defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments are done at baseline and the end of every second cycle (every 8 weeks) thereafter.
- Median Progression-free Survival (PFS) [2 years]
Median PFS will be estimated within each cohort. Progression-free survival is defined as the time in months from the start of protocol treatment until the date of progression or death if death occurred before progression. If the participant is alive and progression-free, PFS will be censored at the date of last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.
- Median Overall Survival (OS) [2 years]
Median OS will be estimated within each cohort. Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histologically confirmed diagnosis of World Health Organization (WHO) grade 4 malignant glioma and radiographic evidence of recurrence or disease progression (as defined by the Response Assessment in Neuro-Oncology (RANO) criteria as a greater than 25% increase in the largest bi-dimensional product of enhancement or a new enhancing lesion, or a significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) abnormality without another co-morbid cause);
-
Age ≥ 18 years;
-
Karnofsky Performance Status ≥ 70%;
-
No more than 3 prior progressions;
-
Cohort 1 only: Non-bevacizumab failure, i.e. either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable within 6 months of prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen, such as:
-
≥ grade 3 hypertension not controlled by medication, hypertensive crisis, or hypertensive encephalopathy
-
≥ grade 3 proteinuria that does not resolve or nephrotic syndrome
-
Any grade GI perforation
-
≥ grade 3 infusion-related reaction
-
≥ grade 3 woundhealing complications
-
≥ grade 3 hemorrhage or any grade central nervous system (CNS) hemorrhage or ≥ grade 2 hemoptysis
-
Any grade arterial thromboembolic event (e.g. myocardial infarction or cerebral infarction) or ≥ grade 3 venous thromboembolic event
-
Any grade posterior reversible encephalopathy syndrome (PRES)
-
≥ grade 3 congestive heart failure
-
≥ grade 2 non-gastrointestinal (GI) abscesses and fistulae;
-
Cohort 2 only: Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment);
-
Pathology consistent with Epidermal Growth Factor Receptor (EGFR)-amplification of tumor (i.e. greater than 15% of cells exhibiting > 5 copies of EGFR loci); archival tissue may be tested for EGFR status in a separate consent;
-
Absolute Neutrophil Count (ANC) ≥ 1,000 cells/µl, platelets ≥ 100,000 cells/µl, hemoglobin ≥ 9 g/dL;
-
Adequate renal function as indicated by the following:
-
Serum creatinine < 1.25 times upper limit of normal or calculated creatinine clearance ≥ 50 ml/min;
-
Urine dipstick for proteinuria < 2+ unless a 24-hour urine protein <1 g of protein is demonstrated;
-
Adequate liver function as indicated by the following:
-
Total bilirubin ≤ 1.6 mg/dL;
-
Aspartate transaminase/alanine transaminase (AST/ALT) ≤ 2.5 x the upper limit of normal (ULN);
-
Magnesium ≥ 0.9 mg/dL;
-
For subjects on corticosteroids, they must be on a stable dose for 7 days prior to anticipated start of study drug;
-
No evidence of > grade 1 active CNS hemorrhage on the baseline magnetic resonance imaging (MRI) or X-ray computed tomography (CT) scan;
-
Signed informed consent approved by the Institutional Review Board prior to patient entry;
-
If the patient is a sexually active female of child bearing potential whose partner is male, or if the patient is a sexually active male whose partner is a female of child bearing potential, the patient must agree to use appropriate contraceptive measures for the duration of the treatment of the tumor and for 6 months afterwards as stated in the informed consent. Female patients of child bearing potential must have a negative serum pregnancy test within 48 hours of starting study treatment;
-
Fertile male subjects must agree to use a medically acceptable contraceptive method (allowed methods of birth control include vasectomy or condom with spermicide) during the trial and for a period of at least 6 months following the last administration of trial drugs.
Exclusion Criteria:
-
Pregnancy or breastfeeding;
-
Prior treatment with EGFR-targeted therapy, including, but not limited to, the following examples: Gilotrif® (afatinib),Tarceva® (erlotinib), Erbitux® (cetuximab), Iressa™ (gefitinib), Vectibix® (panitumumab), Caprelsa® (vandetanib), Tykerb® (lapatinib), CDX110, D2C7-immunotoxin;
-
Active infection requiring intravenous antibiotics within 7 days before enrollment;
-
Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
-
Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation;
-
Treated with immunotherapeutic agents, vaccines, or Mab therapy within 4 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy
-
Treated with alkylating agents within 4 weeks (6 weeks for nitrosoureas) before enrollment or treated within 1 week before enrollment with daily or metronomic chemotherapy, unless the patient has recovered from the expected toxic effects of such therapy to their baseline or to grade 1;
-
Prior treatment (non-alkylating agents) within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy;
-
Known hypersensitivity reactions to any of the components of Sym004;
-
Known current drug abuse or alcohol abuse;
-
Known Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection. Testing is not required as part of this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Preston Robert Tisch Brain Tumor Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Annick Desjardins
- Symphogen A/S
Investigators
- Principal Investigator: Annick Desjardins, MD, FRCPC, Duke University
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- Pro00063483
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 43 patients signed consent and were considered enrolled, however 3 patients withdrew consent prior to treatment and 1 patient was withdrawn by PI prior to treatment. |
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. |
| Period Title: Overall Study | ||||
| STARTED | 20 | 7 | 5 | 7 |
| COMPLETED | 20 | 7 | 5 | 7 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Total of all reporting groups |
| Overall Participants | 20 | 7 | 5 | 7 | 39 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
58.5
|
53
|
61
|
56
|
57.25
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
10
50%
|
3
42.9%
|
0
0%
|
2
28.6%
|
15
38.5%
|
| Male |
10
50%
|
4
57.1%
|
5
100%
|
5
71.4%
|
24
61.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
20
100%
|
6
85.7%
|
5
100%
|
7
100%
|
38
97.4%
|
| Unknown or Not Reported |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
1
2.6%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
5%
|
0
0%
|
0
0%
|
0
0%
|
1
2.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
1
20%
|
0
0%
|
1
2.6%
|
| White |
19
95%
|
7
100%
|
4
80%
|
7
100%
|
37
94.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
20
100%
|
7
100%
|
5
100%
|
7
100%
|
39
100%
|
Outcome Measures
| Title | Six-month Progression-free Survival (PFS6) |
|---|---|
| Description | Within each cohort, the percentage of participants alive and progression-free at 6 months after the start of Sym004 treatment will be determined. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. |
| Measure Participants | 20 | 7 | 5 | 7 |
| Number (95% Confidence Interval) [percentage of participants] |
14.3
71.5%
|
5
71.4%
|
14.3
286%
|
40
571.4%
|
| Title | Percentage of Participants Who Experience Grade 3, 4 or 5 Adverse Events |
|---|---|
| Description | Within each cohort, the percentage of participants who experience grade 3, 4 or 5 adverse events that are possibly, probably or definitely related to study treatment will be calculated. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. |
| Measure Participants | 20 | 7 | 5 | 7 |
| Number [percentage of participants] |
15
75%
|
42.86
612.3%
|
40
800%
|
14.29
204.1%
|
| Title | Radiographic Response |
|---|---|
| Description | Within each cohort, the percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria will be determined. Complete Response (CR) is defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) is defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments are done at baseline and the end of every second cycle (every 8 weeks) thereafter. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. |
| Measure Participants | 20 | 7 | 5 | 7 |
| Number [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Median Progression-free Survival (PFS) |
|---|---|
| Description | Median PFS will be estimated within each cohort. Progression-free survival is defined as the time in months from the start of protocol treatment until the date of progression or death if death occurred before progression. If the participant is alive and progression-free, PFS will be censored at the date of last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. |
| Measure Participants | 20 | 7 | 5 | 7 |
| Median (95% Confidence Interval) [months] |
1.81
|
3.91
|
3.55
|
2.00
|
| Title | Median Overall Survival (OS) |
|---|---|
| Description | Median OS will be estimated within each cohort. Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 18 mg/kg: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004 - 24 mg/kg: Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. |
| Measure Participants | 20 | 7 | 5 | 7 |
| Median (95% Confidence Interval) [months] |
7.54
|
5.51
|
9.95
|
5.39
|
Adverse Events
| Time Frame | From the start of study treatment for a patient until 30 days after treatment is discontinued, maximum of 1 year. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Patients were evaluated for adverse events (all grades), serious adverse events, and adverse events requiring study drug interruption or discontinuation at each study visit for the duration of their participation in the study. | |||||||
| Arm/Group Title | Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg | ||||
| Arm/Group Description | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Sym004: Sym004 was dosed at 18 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Sym004: Sym004 was dosed at 18 mg/kg intravenously every two weeks. . | Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks. Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks. Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks. | ||||
All Cause Mortality |
||||||||
| Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | 7/7 (100%) | 5/5 (100%) | 7/7 (100%) | ||||
Serious Adverse Events |
||||||||
| Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/20 (40%) | 2/7 (28.6%) | 2/5 (40%) | 4/7 (57.1%) | ||||
| Cardiac disorders | ||||||||
| Sinus tachycardia | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| General disorders | ||||||||
| Edema limbs | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Fatigue | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Infections and infestations | ||||||||
| Catheter related infection | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Infections and infestations - Other, Specify: FEVER | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Kidney infection | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Papulopustular rash | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Sepsis | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Injury, poisoning and procedural complications - Other, Specify: CHARGED/HEADBUTTED BY BULL | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscle weakness left-sided | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Muscle weakness right-sided | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Nervous system disorders | ||||||||
| Dysphasia | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Seizure | 4/20 (20%) | 0/7 (0%) | 2/5 (40%) | 1/7 (14.3%) | ||||
| Psychiatric disorders | ||||||||
| Confusion | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Renal and urinary disorders - Other, Specify: NEPHROLITHIASIS | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Rash maculo-papular | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Vascular disorders | ||||||||
| Thromboembolic event | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Non-bevacizumab Failures - 18 mg/kg | Bevacizumab Failures - 18 mg/kg | Non-bevacizumab Failures - 24 mg/kg | Bevacizumab Failures - 24 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | 7/7 (100%) | 5/5 (100%) | 7/7 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 3/20 (15%) | 1/7 (14.3%) | 2/5 (40%) | 1/7 (14.3%) | ||||
| Cardiac disorders | ||||||||
| Cardiac disorders - Other, Specify: TACHYCARDIA | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Sinus bradycardia | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear and labyrinth disorders - Other, Specify: "EAR FULLNESS/SWELLING" FEELING | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Ear and labyrinth disorders - Other, Specify: EAR DISCHARGE | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Ear and labyrinth disorders - Other, Specify: INTERMITTENT FEELING OF WATER IN EARS | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Ear pain | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Tinnitus | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Eye disorders | ||||||||
| Blurred vision | 1/20 (5%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Conjunctivitis | 1/20 (5%) | 1/7 (14.3%) | 1/5 (20%) | 0/7 (0%) | ||||
| Dry eye | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Eye disorders - Other, Specify: "BLURRED", EYES CLOSED MOST TIMES | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Eye disorders - Other, Specify: DECREASED VISION | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Eye disorders - Other, Specify: DIPLOPIA | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Eye disorders - Other, Specify: EYELID ITCHING, RIGHT EYE REDNESS, CRUSTING TO EYES | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Eye disorders - Other, Specify: HEMIANOPIA | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Eye disorders - Other, Specify: L EYE WITH DRAINAGE; CRUST AROUND EYELID | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Anal hemorrhage | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Constipation | 3/20 (15%) | 1/7 (14.3%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Diarrhea | 4/20 (20%) | 1/7 (14.3%) | 2/5 (40%) | 0/7 (0%) | ||||
| Dry mouth | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Dyspepsia | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Dysphagia | 2/20 (10%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Fecal incontinence | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Gastroesophageal reflux disease | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Gastrointestinal disorders - Other, Specify: GLOSSITIS | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Gastrointestinal disorders - Other, Specify: HYPERSALIVATION | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Gastrointestinal disorders - Other, Specify: MOUTH SORES | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Hemorrhoidal hemorrhage | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Mucositis oral | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Nausea | 4/20 (20%) | 0/7 (0%) | 1/5 (20%) | 1/7 (14.3%) | ||||
| Oral hemorrhage | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Oral pain | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Rectal hemorrhage | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Vomiting | 3/20 (15%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| General disorders | ||||||||
| Chills | 0/20 (0%) | 0/7 (0%) | 2/5 (40%) | 0/7 (0%) | ||||
| Edema face | 1/20 (5%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Edema limbs | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Fatigue | 7/20 (35%) | 2/7 (28.6%) | 3/5 (60%) | 2/7 (28.6%) | ||||
| Flu like symptoms | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Gait disturbance | 1/20 (5%) | 1/7 (14.3%) | 1/5 (20%) | 0/7 (0%) | ||||
| General disorders and administration site conditions - Other, Specify: CHILLS | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| General disorders and administration site conditions - Other, Specify: RUNNY NOSE | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Infusion related reaction | 3/20 (15%) | 2/7 (28.6%) | 1/5 (20%) | 2/7 (28.6%) | ||||
| Irritability | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Pain | 4/20 (20%) | 0/7 (0%) | 2/5 (40%) | 2/7 (28.6%) | ||||
| Infections and infestations | ||||||||
| Infections and infestations - Other, Specify: BACTEREMIA | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Infections and infestations - Other, Specify: FUNGAL RASH | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Infections and infestations - Other, Specify: MRSA INFECTION | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Mucosal infection | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Otitis media | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Papulopustular rash | 2/20 (10%) | 1/7 (14.3%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Paronychia | 0/20 (0%) | 1/7 (14.3%) | 1/5 (20%) | 0/7 (0%) | ||||
| Rash pustular | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Sinusitis | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin infection | 3/20 (15%) | 1/7 (14.3%) | 1/5 (20%) | 0/7 (0%) | ||||
| Soft tissue infection | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Upper respiratory infection | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Urinary tract infection | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Vaginal infection | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Burn | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Fall | 4/20 (20%) | 0/7 (0%) | 1/5 (20%) | 1/7 (14.3%) | ||||
| Injury, poisoning and procedural complications - Other, Specify: LACERATION TO RIGHT LOWER LEG | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Injury, poisoning and procedural complications - Other, Specify: WOUND FROM FALL; DRAINAGE | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 3/20 (15%) | 2/7 (28.6%) | 0/5 (0%) | 2/7 (28.6%) | ||||
| Alkaline phosphatase increased | 4/20 (20%) | 2/7 (28.6%) | 1/5 (20%) | 0/7 (0%) | ||||
| Aspartate aminotransferase increased | 1/20 (5%) | 1/7 (14.3%) | 1/5 (20%) | 2/7 (28.6%) | ||||
| Creatinine increased | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Lymphocyte count decreased | 5/20 (25%) | 1/7 (14.3%) | 1/5 (20%) | 2/7 (28.6%) | ||||
| Neutrophil count decreased | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 2/7 (28.6%) | ||||
| Platelet count decreased | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 4/7 (57.1%) | ||||
| Weight loss | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| White blood cell decreased | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 3/20 (15%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Dehydration | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Hyperglycemia | 8/20 (40%) | 2/7 (28.6%) | 4/5 (80%) | 3/7 (42.9%) | ||||
| Hypoalbuminemia | 11/20 (55%) | 3/7 (42.9%) | 3/5 (60%) | 2/7 (28.6%) | ||||
| Hypocalcemia | 8/20 (40%) | 3/7 (42.9%) | 4/5 (80%) | 4/7 (57.1%) | ||||
| Hypoglycemia | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Hypokalemia | 8/20 (40%) | 2/7 (28.6%) | 1/5 (20%) | 1/7 (14.3%) | ||||
| Hypomagnesemia | 13/20 (65%) | 5/7 (71.4%) | 4/5 (80%) | 3/7 (42.9%) | ||||
| Hyponatremia | 2/20 (10%) | 1/7 (14.3%) | 2/5 (40%) | 0/7 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Generalized muscle weakness | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Muscle weakness left-sided | 1/20 (5%) | 2/7 (28.6%) | 1/5 (20%) | 0/7 (0%) | ||||
| Muscle weakness right-sided | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/20 (5%) | 0/7 (0%) | 1/5 (20%) | 2/7 (28.6%) | ||||
| Dysphasia | 3/20 (15%) | 1/7 (14.3%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Headache | 7/20 (35%) | 2/7 (28.6%) | 2/5 (40%) | 0/7 (0%) | ||||
| Memory impairment | 0/20 (0%) | 1/7 (14.3%) | 1/5 (20%) | 2/7 (28.6%) | ||||
| Nervous system disorders - Other, Specify: DIFFICULTY HOLDING ITEMS WITH HIS LEFT HAND | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Nervous system disorders - Other, Specify: DISORIENTATION | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Nervous system disorders - Other, Specify: WEAKNESS, BALANCE OFF | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Neuralgia | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Paresthesia | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 2/7 (28.6%) | ||||
| Pyramidal tract syndrome | 1/20 (5%) | 0/7 (0%) | 1/5 (20%) | 1/7 (14.3%) | ||||
| Seizure | 6/20 (30%) | 4/7 (57.1%) | 2/5 (40%) | 1/7 (14.3%) | ||||
| Tremor | 0/20 (0%) | 1/7 (14.3%) | 2/5 (40%) | 0/7 (0%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Confusion | 1/20 (5%) | 0/7 (0%) | 1/5 (20%) | 3/7 (42.9%) | ||||
| Depression | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Insomnia | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Libido decreased | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Suicidal ideation | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Hematuria | 2/20 (10%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Proteinuria | 0/20 (0%) | 2/7 (28.6%) | 1/5 (20%) | 0/7 (0%) | ||||
| Renal and urinary disorders - Other, Specify: DISCOLORED URINE | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Urinary incontinence | 1/20 (5%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Allergic rhinitis | 0/20 (0%) | 1/7 (14.3%) | 1/5 (20%) | 0/7 (0%) | ||||
| Cough | 1/20 (5%) | 0/7 (0%) | 2/5 (40%) | 0/7 (0%) | ||||
| Dyspnea | 1/20 (5%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Nasal congestion | 1/20 (5%) | 2/7 (28.6%) | 0/5 (0%) | 0/7 (0%) | ||||
| Postnasal drip | 2/20 (10%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Sore throat | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 2/20 (10%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Dry skin | 5/20 (25%) | 1/7 (14.3%) | 1/5 (20%) | 0/7 (0%) | ||||
| Hirsutism | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Pain of skin | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Pruritus | 2/20 (10%) | 0/7 (0%) | 4/5 (80%) | 1/7 (14.3%) | ||||
| Rash acneiform | 3/20 (15%) | 0/7 (0%) | 2/5 (40%) | 2/7 (28.6%) | ||||
| Rash maculo-papular | 13/20 (65%) | 6/7 (85.7%) | 4/5 (80%) | 4/7 (57.1%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: INDEX FINGER CUTICLE REDNESS/IRRITATION | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: "BRUISING APPEARANCE" | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: "REDNESS TO CHEEKS" | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: FACIAL REDNESS | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: HEELS CRACKED WITH SCABBING AND BRUISING | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: RASH | 3/20 (15%) | 1/7 (14.3%) | 1/5 (20%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: RED PATCHY SPOTS/WHITE HEAD ON NOSE | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: SENSITIVE FEET | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: SKIN TEARS | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: SKIN TRAUMA | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: SOME NAILBEDS OF FINGERS REDDENED | 0/20 (0%) | 0/7 (0%) | 0/5 (0%) | 1/7 (14.3%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: SORE, INFLAMED AREA BEHIND L EAR | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 0/7 (0%) | ||||
| Skin and subcutaneous tissue disorders - Other, Specify: SUNBURN | 0/20 (0%) | 1/7 (14.3%) | 0/5 (0%) | 0/7 (0%) | ||||
| Skin ulceration | 1/20 (5%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/20 (0%) | 0/7 (0%) | 1/5 (20%) | 1/7 (14.3%) | ||||
| Hypotension | 2/20 (10%) | 0/7 (0%) | 0/5 (0%) | 0/7 (0%) | ||||
| Thromboembolic event | 0/20 (0%) | 2/7 (28.6%) | 0/5 (0%) | 0/7 (0%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Principal Investigator |
|---|---|
| Organization | Duke University Medical Center |
| Phone | 9196845301 |
| dukebrain1@duke.edu |
- Pro00063483