Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax
Study Details
Study Description
Brief Summary
The study will be a multi-center, prospective, randomized, single-blinded, placebo-controlled Phase II trial of Herceptin + NeuVax(TM) vaccine (E75 peptide/granulocyte macrophage-colony stimulating factor) (GM-CSF) versus Herceptin + GM-CSF alone. The target study population is node-positive (NP) (or node-negative [NN] if negative for both ER and PR) breast cancer patients with HER2 1+ and 2+ expressing tumors who are disease-free after standard of care therapy. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA-typed. E75 is a CD8-eliciting peptide vaccine that was restricted to HLA-A2+ or HLA-A3+ patients (approximately two-thirds of the US population), and has been extended to HLA-A24+ and HLA-A26+ as well.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
In this study, the investigators intend to assess the ability of the combination of Herceptin and NeuVax vaccine (HER2 protein E75 peptide administered with the immunoadjuvant GM-CSF) given in the adjuvant setting to prevent recurrences in NP (or NN if negative for both estrogen (ER) and progesterone (PR) receptors) breast cancer patients with tumors that express low (1+) or intermediate (2+) levels of HER2. Enrolled patients will be randomized to receive Herceptin and NeuVax vaccine or Herceptin with GM-CSF alone (no NeuVax vaccine). The safety of the combination therapy will be documented, specifically to ensure that no additive cardiac toxicity results from combination HER2-directed therapy. Efficacy will be documented by comparing the DFS and immunological responses between treatment groups.
The primary efficacy endpoint is to compare DFS at 24 months between treatment groups. The primary safety issue is to prove there is no additive cardiac toxicity with combination HER2-directed therapy. A secondary endpoint of the trial is to compare DFS at 36 months. Immunologic responses to the vaccine will also be documented and correlated to clinical benefit.
The study will be a multi-center, prospective, randomized, single-blinded, placebo-controlled Phase II trial of Herceptin + NeuVax vaccine versus Herceptin + GM-CSF alone. The target study population is NP (or NN if negative for both ER and PR) breast cancer patients with HER2 1+ and 2+ expressing tumors who are disease-free after standard of care therapy. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA-typed. E75 is a CD8-eliciting peptide vaccine that is restricted to HLA-A2+ or HLA-A3+ patients (approximately two-thirds of the US population), and has been extended to HLA-A24+ and HLA-A26+ as well.
HLA-A2+/A3+/A24+/or A26+ patients who meet all other eligibility criteria will be randomized to receive Herceptin + NeuVax vaccine or Herceptin + GM-CSF alone. For both groups, Herceptin will be given every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy. The first Herceptin infusion must be given no sooner than three weeks and no later than 12 weeks after completion of chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Herceptin will be administered as described in Section 4.3. Patients randomized to the NeuVax vaccine arm will receive vaccinations of E75 peptide (1000 mcg) and GM-CSF (250 mcg) administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion. In extenuating circumstances, the first vaccination may be delayed to the fourth or fifth Herceptin infusion with prior approval from the Principal Investigator. Those patients randomized to the GM-CSF alone arm will receive vaccinations of GM-CSF (250 mcg) administered in an identical manner to those receiving NeuVax vaccine. Patients will be blinded as to whether they are receiving NeuVax vaccine or GM-CSF alone.
Upon completion of the vaccination series, booster inoculations (same dose and route) will be administered every six months x4 for total combination (Herceptin and vaccine) treatment duration of 30 months. The first booster inoculation will occur with the final Herceptin infusion, with subsequent boosters timed every six months from the first booster. Booster inoculations will occur for patients randomized to receive E75/GM-CSF as well as patients randomized to receive GM-CSF alone, and will consist of the same treatment drugs and dosing (i.e. E75/GM-CSF patients will be boosted with E75/GM-CSF while GM-CSF alone patients will be boosted with GM-CSF alone). Patient blinding will be maintained throughout the study.
Subjects will be followed for safety issues, immunologic response and clinical recurrence. Patients will be monitored 48-72 hours after each inoculation for reaction to the inoculation as well as documentation of any adverse effects experienced. Immunologic response will be documented with both in vitro phenotypic and functional assays as well as in vivo delayed type hypersensitivity (DTH) reactions. All patients will be followed for a total of 36 months to document disease-free status.
The investigators plan to enroll 300 patients (150 in each treatment arm) at a planned accrual rate of 12 patients per month (approximately one per study site per month). With accrual beginning in April, 2013, enrollment of the last patient would be expected in August 2017 followed by a three-year follow-up period. The duration of the trial is expected to be seven years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Herceptin + NeuVax vaccine Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. Patients will be blinded regarding assigned arm. After completion of primary vaccine series, patients will receive 4 NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. |
Drug: Herceptin
Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy. The first Herceptin infusion will be given no sooner than three weeks and no later than 12 weeks after completion of chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk.
Other Names:
Drug: NeuVax vaccine
At the time of vaccine administration, a frozen solution of E75 acetate (1.5mg/ml) is thawed and 1000mcg E75 peptide mixed thoroughly with 250mcg GM-CSF. This constitutes the NeuVax vaccine. For patients randomized to the Herceptin + NeuVax vaccine arm, they will commence Herceptin monotherapy and then will begin the NeuVax vaccine series immediately after completion of the third Herceptin infusion. The vaccine series consists of NeuVax vaccine administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion.
Other Names:
Drug: GM-CSF
For patients randomized to the Herceptin + GM-CSF only arm, they will commence Herceptin monotherapy and then will begin the GM-CSF inoculation series immediately after completion of the third Herceptin infusion. The GM-CSF inoculation series consists of 250mcg GM-CSF administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion.
Other Names:
|
| Active Comparator: Herceptin + GM-CSF only Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. Patients will be blinded as to whether they are receiving NeuVax vaccine or GM-CSF only. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. |
Drug: Herceptin
Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy. The first Herceptin infusion will be given no sooner than three weeks and no later than 12 weeks after completion of chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk.
Other Names:
Drug: GM-CSF
For patients randomized to the Herceptin + GM-CSF only arm, they will commence Herceptin monotherapy and then will begin the GM-CSF inoculation series immediately after completion of the third Herceptin infusion. The GM-CSF inoculation series consists of 250mcg GM-CSF administered intradermally every three weeks for six total vaccinations, 30-120 minutes after completion of Herceptin infusion.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Disease-free Survival (DFS) [Disease-free survival at 24 months]
Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur every three months for the first 24 months after completion of primary therapies and every six months thereafter with clinical exam, and laboratory and radiographic surveillance. The primary objective of the study is disease-free survival (DFS) at 24 months.
- Disease-free Survival (DFS) [Disease-free survival up to 36 months]
Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur at months 30 and 36 after completion of primary therapies with clinical exam, and laboratory and radiographic surveillance. The secondary objective of the study is disease-free survival (DFS) at 36 months.
Secondary Outcome Measures
- Percent Ejection Fraction - A Measure of Cardiac Toxicity [24 months]
Each patient, regardless of randomization, will undergo cardiac assessment (ejection fraction) of Multiple Gated Acquisition scan (MUGA) preferred, echocardiogram (ECHO) allowed, consistency required) at baseline, 3 months, 6 months, 12 months, and 24 months. Cardiac assessment will continue every six months if a patient experiences a greater than 10% reduction from baseline for the duration of the trial or until resolution.
- Local and Systemic Toxicities [Duration of vaccine or inoculation series and booster series, an average of 30 months.]
Standard local and systemic toxicities will be collected and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 toxicity scale. For both the regular and booster inoculations, patients will be monitored closely for one hour after inoculation with questioning, serial exams and vital signs every 15 minutes to observe for a hypersensitivity reaction. Patients will also return to the clinic 48-72 hours after each inoculation for questioning regarding systemic toxicity and to examine and measure the local reaction at the inoculation sites. Reported are the maximum related and graded adverse events per patient.
Eligibility Criteria
Criteria
Patients will be included in the study based on the following criteria:
-
Women 18 years or older
-
Node-positive breast cancer (AJCC N1, N2, or N3)
-
Node-negative breast cancer if negative for both estrogen (ER) and progesterone (PR) receptors and have received chemotherapy as standard of care
-
Clinically cancer-free (no evidence of disease) after standard of care therapy (surgery, chemotherapy, radiation therapy as directed by NCCN guidelines). Hormonal therapy will continue per standard of care. Neoadjuvant chemotherapy is allowed.
-
Recovery from any toxicity(ies) associated with prior adjuvant therapy.
-
HER2 expression of 1+ or 2+ by IHC. FISH or Dual-ISH testing must be performed on IHC 2+ tumors and shown to be non-amplified by FISH (≤2.0) or by Dual-ISH (≤2.0).
-
HLA-A2, A3, A24, or A26 positive
-
LVEF >50%, or an LVEF within the normal limits of the institution's specific testing (MUGA or Echo)
-
ECOG 0,1
-
Signed informed consent
-
Adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)
-
Must start study treatment (receive first Herceptin infusion) 15between 3-12 weeks from completion of standard of care therapy.
4.1.3 Exclusion Criteria
Patients will be excluded from the study based on the following criteria:
-
Node-negative breast cancer (AJCC N0 or N0(i+)) unless negative for both estrogen (ER) and progesterone (PR) receptors and has received chemotherapy as standard of care
-
Clinical or radiographic evidence of distant or residual breast cancer
-
HER2 negative (IHC 0) or HER2 3+ or FISHDual-ISH amplified (FISH >2.0); Dual-ISH >2.0
-
HLA-A2, A3, A24, A26 negative
-
History of prior Herceptin therapy
-
NYHA stage 3 or 4 cardiac disease
-
LVEF <50%, or less than the normal limits of the institution's specific testing (MUGA or Echo)
-
Immune deficiency disease or HIV, HBV, HCV
-
Receiving immunosuppressive therapy including chemotherapy, chronic steroids, methotrexate, or other known immunosuppressive agents
-
ECOG ≥2
-
Tbili >1.8, creatinine>2, hemoglobin<10, platelets<50,000, WBC<2,000
-
Pregnancy (assessed by urine HCG)
-
Breast feeding
-
Any active autoimmune disease requiring treatment, with the exception of vitiligo
-
Active pulmonary disease requiring medication to include multiple inhalers
-
Involved in other experimental protocols (except with permission of the other study PI)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Samuel Oschin Comprehensive Cancer Institute - Cedars Sinai Medical Center | Beverly Hills | California | United States | 90211 |
| 2 | Sarcoma Oncology Research Center, LLC | Santa Monica | California | United States | 90403 |
| 3 | St. Joseph Heritage Healthcare | Santa Rosa | California | United States | 95403 |
| 4 | Sibley Memorial Hospital | Washington | District of Columbia | United States | 20016 |
| 5 | Katzen Cancer Research Center, George Washington University | Washington | District of Columbia | United States | 20037 |
| 6 | University of Miami | Deerfield Beach | Florida | United States | 33442 |
| 7 | University of Miami | Kendall | Florida | United States | 33176 |
| 8 | University of Miami | Miami | Florida | United States | 33136 |
| 9 | Florida Cancer Research Institute | Plantation | Florida | United States | 33324 |
| 10 | University of Miami | Plantation | Florida | United States | 33324 |
| 11 | H. Lee Moffitt Cancer Center & Research Institute, Inc | Tampa | Florida | United States | 33612 |
| 12 | University of Hawaii Cancer Center | Honolulu | Hawaii | United States | 96813 |
| 13 | Franciscan Health Indianapolis | Indianapolis | Indiana | United States | 46237 |
| 14 | Memorial Hospital of South Bend | South Bend | Indiana | United States | 46601 |
| 15 | Cancer Center of Kansas | Wichita | Kansas | United States | 67212 |
| 16 | Medstar Health - Union Memorial Hospital | Baltimore | Maryland | United States | 21218-2895 |
| 17 | Medstar Health - Weinberg Cancer Institute at Franklin Square | Baltimore | Maryland | United States | 21237 |
| 18 | MedStar Health - Good Samaritan Hospital | Baltimore | Maryland | United States | 21239 |
| 19 | The Valley Hospital | Paramus | New Jersey | United States | 07652 |
| 20 | North Shore Hematology Oncology Associates | Bronx | New York | United States | 10469 |
| 21 | Tisch Cancer Institute/Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 22 | Legacy Health, Legacy Good Samaritan Medical Center | Portland | Oregon | United States | 97210 |
| 23 | Thomas Jefferson University - Kimmel Cancer Center | Philadelphia | Pennsylvania | United States | 19107 |
| 24 | University of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 25 | Texas Oncology (Cancer Care Centers of South Texas) | San Antonio | Texas | United States | 78217 |
| 26 | Virginia Cancer Specialists | Fairfax | Virginia | United States | 22031 |
| 27 | Providence Regional Medical Center | Everett | Washington | United States | 98201 |
| 28 | Swedish Cancer Institute | Seattle | Washington | United States | 98104 |
| 29 | Columbia St. Mary's | Milwaukee | Wisconsin | United States | 53211 |
Sponsors and Collaborators
- George E. Peoples
- Genentech, Inc.
- Sellas Life Sciences Group
Investigators
- Principal Investigator: COL (ret.) George E. Peoples, MD, FACS, Cancer Insight, LLC
- Study Director: COL (ret.) George E. Peoples, MD, FACS, Cancer Insight, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- 368255
- 1137008 / 20130058
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only |
|---|---|---|
| Arm/Group Description | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. |
| Period Title: Overall Study | ||
| STARTED | 136 | 139 |
| Primary Vaccine Series Completed | 121 | 132 |
| Booster Series Completed | 40 | 30 |
| COMPLETED | 18 | 17 |
| NOT COMPLETED | 118 | 122 |
Baseline Characteristics
| Arm/Group Title | Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only | Total |
|---|---|---|---|
| Arm/Group Description | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. | Total of all reporting groups |
| Overall Participants | 136 | 139 | 275 |
| Age (years) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [years] |
52.2
|
50.5
|
51.6
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
136
100%
|
139
100%
|
275
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
109
80.1%
|
97
69.8%
|
206
74.9%
|
| Asian |
2
1.5%
|
9
6.5%
|
11
4%
|
| Black |
13
9.6%
|
20
14.4%
|
33
12%
|
| Hispanic |
10
7.4%
|
9
6.5%
|
19
6.9%
|
| Unknown |
2
1.5%
|
4
2.9%
|
6
2.2%
|
| Nottingham modified, Scarff-Bloom-Richardson Grade (Count of Participants) | |||
| Grade 1 |
8
5.9%
|
14
10.1%
|
22
8%
|
| Grade 2 |
57
41.9%
|
56
40.3%
|
113
41.1%
|
| Grade 3 |
69
50.7%
|
69
49.6%
|
138
50.2%
|
| Hormone receptor status (Count of Participants) | |||
| ER Positive |
81
59.6%
|
95
68.3%
|
176
64%
|
| PR Positive |
77
56.6%
|
83
59.7%
|
160
58.2%
|
| Triple Negative |
53
39%
|
44
31.7%
|
97
35.3%
|
| HER2 Immunohistochemistry (IHC) (Count of Participants) | |||
| IHC 1+ |
89
65.4%
|
89
64%
|
178
64.7%
|
| IHC 2+ |
47
34.6%
|
50
36%
|
97
35.3%
|
| Breast surgery (Count of Participants) | |||
| Breast Conservation Therapy |
39
28.7%
|
34
24.5%
|
73
26.5%
|
| Mastectomy |
97
71.3%
|
104
74.8%
|
201
73.1%
|
| None |
0
0%
|
1
0.7%
|
1
0.4%
|
| Chemotherapy (Count of Participants) | |||
| Neoadjuvant |
72
52.9%
|
76
54.7%
|
148
53.8%
|
| Adjuvant |
59
43.4%
|
57
41%
|
116
42.2%
|
| None |
5
3.7%
|
6
4.3%
|
11
4%
|
| Radiation with Breast Conservation Therapy (Count of Participants) | |||
| Adjuvant |
39
28.7%
|
34
24.5%
|
73
26.5%
|
| None |
0
0%
|
0
0%
|
0
0%
|
| Radiation with Mastectomy (Count of Participants) | |||
| Adjuvant |
76
55.9%
|
89
64%
|
165
60%
|
| Neoadjuvant |
2
1.5%
|
0
0%
|
2
0.7%
|
| None |
19
14%
|
15
10.8%
|
34
12.4%
|
| Axillary Surgery (Count of Participants) | |||
| Axillary Dissection |
81
59.6%
|
88
63.3%
|
169
61.5%
|
| Sentinel Lymph Node Biopsy |
55
40.4%
|
48
34.5%
|
103
37.5%
|
| None |
0
0%
|
3
2.2%
|
3
1.1%
|
| AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) (Count of Participants) | |||
| Unknown |
1
0.7%
|
2
1.4%
|
3
1.1%
|
| 0 |
0
0%
|
1
0.7%
|
1
0.4%
|
| I |
4
2.9%
|
3
2.2%
|
7
2.5%
|
| IIA |
16
11.8%
|
13
9.4%
|
29
10.5%
|
| IIB |
19
14%
|
18
12.9%
|
37
13.5%
|
| IIIA |
14
10.3%
|
25
18%
|
39
14.2%
|
| IIIB |
7
5.1%
|
2
1.4%
|
9
3.3%
|
| IIIC |
10
7.4%
|
13
9.4%
|
23
8.4%
|
| IV* |
1
0.7%
|
0
0%
|
1
0.4%
|
| AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) (Count of Participants) | |||
| Unknown |
1
0.7%
|
0
0%
|
1
0.4%
|
| 0 |
5
3.7%
|
4
2.9%
|
9
3.3%
|
| I |
11
8.1%
|
9
6.5%
|
20
7.3%
|
| IIA |
16
11.8%
|
15
10.8%
|
31
11.3%
|
| IIB |
12
8.8%
|
11
7.9%
|
23
8.4%
|
| IIIA |
11
8.1%
|
20
14.4%
|
31
11.3%
|
| IIIB |
4
2.9%
|
3
2.2%
|
7
2.5%
|
| IIIC |
12
8.8%
|
14
10.1%
|
26
9.5%
|
| AJCC, 7th Edition, Pathologic Stage (Count of Participants) | |||
| I |
10
7.4%
|
9
6.5%
|
19
6.9%
|
| IIA |
11
8.1%
|
12
8.6%
|
23
8.4%
|
| IIB |
14
10.3%
|
14
10.1%
|
28
10.2%
|
| IIIA |
21
15.4%
|
18
12.9%
|
39
14.2%
|
| IIIB |
0
0%
|
0
0%
|
0
0%
|
| IIIC |
8
5.9%
|
10
7.2%
|
18
6.5%
|
Outcome Measures
| Title | Disease-free Survival (DFS) |
|---|---|
| Description | Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur every three months for the first 24 months after completion of primary therapies and every six months thereafter with clinical exam, and laboratory and radiographic surveillance. The primary objective of the study is disease-free survival (DFS) at 24 months. |
| Time Frame | Disease-free survival at 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only |
|---|---|---|
| Arm/Group Description | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. |
| Measure Participants | 136 | 139 |
| Number [Percentage of participants who survived] |
89.8
66%
|
83.8
60.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Kaplan-Meier Survival Analysis | |
| Statistical Test of Hypothesis | p-Value | 0.18 |
| Comments | ||
| Method | Kaplan-Meier Survival Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.62 | |
| Confidence Interval |
(2-Sided) 95% .31 to 1.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Disease-free Survival (DFS) |
|---|---|
| Description | Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur at months 30 and 36 after completion of primary therapies with clinical exam, and laboratory and radiographic surveillance. The secondary objective of the study is disease-free survival (DFS) at 36 months. |
| Time Frame | Disease-free survival up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only |
|---|---|---|
| Arm/Group Description | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. |
| Measure Participants | 136 | 139 |
| Number [Percent Survival] |
86.7
|
80.8
|
| Title | Percent Ejection Fraction - A Measure of Cardiac Toxicity |
|---|---|
| Description | Each patient, regardless of randomization, will undergo cardiac assessment (ejection fraction) of Multiple Gated Acquisition scan (MUGA) preferred, echocardiogram (ECHO) allowed, consistency required) at baseline, 3 months, 6 months, 12 months, and 24 months. Cardiac assessment will continue every six months if a patient experiences a greater than 10% reduction from baseline for the duration of the trial or until resolution. |
| Time Frame | 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on those patients with data at each specified time point. |
| Arm/Group Title | Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only |
|---|---|---|
| Arm/Group Description | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. |
| Measure Participants | 136 | 137 |
| Baseline |
60.82
(.61)
|
61.47
(.47)
|
| 3 Months |
59.49
(.54)
|
59.56
(.54)
|
| 6 Months |
59.92
(.88)
|
60.07
(.57)
|
| 12 Months |
59.39
(.56)
|
59.7
(.57)
|
| 24 Months |
61.05
(.79)
|
61.09
(.78)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.02 |
| Comments | Comparison of the mean LVEF from baseline to 3 months, 6 months, and 12 months; this time period includes the therapy period of trastuzumab. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.58 |
| Comments | The mean LVEF compared at baseline to 3 months, 6 months, 12 months and 24 months; this time period includes the duration of trastuzumab therapy and 1 year after completion of trastuzumab therapy. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.65 |
| Comments | Evaluating LVEF at all time points with a linear mixed regression model, this analysis compared cardiac ejection fraction over time. | |
| Method | Regression, Linear | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.91 |
| Comments | This analysis evaluated LVEF at all time points with a linear mixed regression model between randomization arms. | |
| Method | Regression, Linear | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.81 |
| Comments | This analysis evaluated LVEF at all time points with a linear mixed regression model between the arms over time. | |
| Method | Regression, Linear | |
| Comments | ||
| Title | Local and Systemic Toxicities |
|---|---|
| Description | Standard local and systemic toxicities will be collected and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 toxicity scale. For both the regular and booster inoculations, patients will be monitored closely for one hour after inoculation with questioning, serial exams and vital signs every 15 minutes to observe for a hypersensitivity reaction. Patients will also return to the clinic 48-72 hours after each inoculation for questioning regarding systemic toxicity and to examine and measure the local reaction at the inoculation sites. Reported are the maximum related and graded adverse events per patient. |
| Time Frame | Duration of vaccine or inoculation series and booster series, an average of 30 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis was performed only on patients that received NeuVax or Control. |
| Arm/Group Title | Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only |
|---|---|---|
| Arm/Group Description | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. |
| Measure Participants | 129 | 132 |
| Local Grade 1 |
82.3
|
55.7
|
| Local Grade 2 |
15.0
|
33.0
|
| Local Grade 3 |
2.7
|
11.3
|
| Systemic Grade 1 |
79.6
|
58.5
|
| Systemic Grade 2 |
20.4
|
30.2
|
| Systemic Grade 3 |
0
|
11.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | The safety group consisted of any patients who received NPS with GM-CSF or placebo with GM-CSF inoculations. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.149 |
| Comments | ||
| Method | Chi-squared | |
| Comments | Comparison of the maximum related local toxicity experienced per patient and compared between treatment arms. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.901 |
| Comments | ||
| Method | Chi-squared | |
| Comments | Comparison of the maximum related systemic toxicity experienced per patient and compared between treatment arms. | |
Adverse Events
| Time Frame | The duration of the trial, up to 36 months. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only | ||
| Arm/Group Description | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. | Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. | ||
All Cause Mortality |
||||
| Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/136 (0.7%) | 0/139 (0%) | ||
Serious Adverse Events |
||||
| Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/136 (10.3%) | 12/139 (8.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Cardiac disorders | ||||
| Atrial fibrillation | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Heart failure | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 2 |
| Sinus tachycardia | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Gastrointestinal disorders | ||||
| Colonic hemorrhage | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Esophageal obstruction | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Pancreatitis | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| General disorders | ||||
| Fever | 1/136 (0.7%) | 2 | 0/139 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Other, specify | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Immune system disorders | ||||
| Allergic reaction | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Infections and infestations | ||||
| Skin Infection | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Breast infection | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Device related infection | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Skin Infection | 1/136 (0.7%) | 2 | 0/139 (0%) | 0 |
| Soft tissue infection | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Wound infection | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Fracture | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Spinal fracture | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Wound complication | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Investigations | ||||
| Creatinine increased | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Metabolism and nutrition disorders | ||||
| Hyperglycemia | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Other, specify | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Nervous system disorders | ||||
| Edema cerebral | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Seizure | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Syncope | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Renal and urinary disorders | ||||
| Urinary tract obstruction | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Other, specify | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Vascular disorders | ||||
| Thromboembolic event | 2/136 (1.5%) | 2 | 2/139 (1.4%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Herceptin + NeuVax Vaccine | Herceptin + GM-CSF Only | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 136/ (NaN) | 139/ (NaN) | ||
| Blood and lymphatic system disorders | ||||
| Other, specify | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Anemia | 5/136 (3.7%) | 12 | 5/139 (3.6%) | 5 |
| Cardiac disorders | ||||
| Other, specify | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Palpitations | 4/136 (2.9%) | 4 | 6/139 (4.3%) | 6 |
| Left ventricular systolic dysfunction | 3/136 (2.2%) | 3 | 4/139 (2.9%) | 4 |
| Right ventricular dysfunction | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Heart failure | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Supraventricular tachycardia | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Sinus tachycardia | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Atrial flutter | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Atrial fibrillation | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Aortic valve disease | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Other, specify | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Tinnitus | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Tinnitus | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Vertigo | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Hearing impaired | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Ear pain | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Endocrine disorders | ||||
| Other, specify | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Hypothyroidism | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Hyperthyroidism | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Eye disorders | ||||
| Other, specify | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Watering eyes | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Uveitis | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Eyelid function disorder | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Other, specify | 4/136 (2.9%) | 5 | 1/139 (0.7%) | 4 |
| Watering eyes | 1/136 (0.7%) | 1 | 4/139 (2.9%) | 4 |
| Blurred vision | 1/136 (0.7%) | 6 | 0/139 (0%) | 0 |
| Floaters | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Conjuctivitis | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Optic nerve disorder | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Dry eye | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Cataract | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Gastrointestinal disorders | ||||
| Nausea | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Other, specify | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Diarrhea | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Abdominal pain | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Anal hemorrhage | 1/136 (0.7%) | 2 | 0/139 (0%) | 0 |
| Toothache | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Dental abscess | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Chelitis | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Nausea | 38/136 (27.9%) | 87 | 38/139 (27.3%) | 88 |
| Other, specify | 8/136 (5.9%) | 9 | 3/139 (2.2%) | 4 |
| Diarrhea | 25/136 (18.4%) | 48 | 16/139 (11.5%) | 29 |
| Abdominal pain | 8/136 (5.9%) | 9 | 7/139 (5%) | 13 |
| Vomiting | 9/136 (6.6%) | 11 | 10/139 (7.2%) | 12 |
| Constipation | 6/136 (4.4%) | 11 | 7/139 (5%) | 7 |
| GERD | 4/136 (2.9%) | 4 | 7/139 (5%) | 10 |
| Dyspepsia | 4/136 (2.9%) | 5 | 6/139 (4.3%) | 6 |
| Mucositis oral | 2/136 (1.5%) | 2 | 4/139 (2.9%) | 5 |
| Bloating | 2/136 (1.5%) | 2 | 2/139 (1.4%) | 2 |
| Flatulence | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Oral pain | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Hemorrhoids | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Pancreatitis | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Esophageal obstruction | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Dry mouth | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Colonic hemorrhage | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Colitis | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| General disorders | ||||
| Injection site reaction | 109/136 (80.1%) | 846 | 102/139 (73.4%) | 698 |
| Fatigue | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Pain | 49/136 (36%) | 140 | 32/139 (23%) | 83 |
| Other, specify | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Malaise | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Chills | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Flu like symptoms | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Edema limbs | 1/136 (0.7%) | 4 | 2/139 (1.4%) | 3 |
| Infusion related reaction | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Localized edema | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Facial pain | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Injection site reaction | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Fatigue | 70/136 (51.5%) | 236 | 69/139 (49.6%) | 188 |
| Pain | 3/136 (2.2%) | 3 | 4/139 (2.9%) | 4 |
| Other, specify | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Malaise | 30/136 (22.1%) | 79 | 28/139 (20.1%) | 64 |
| Chills | 29/136 (21.3%) | 55 | 29/139 (20.9%) | 52 |
| Flu like symptoms | 23/136 (16.9%) | 36 | 26/139 (18.7%) | 38 |
| Fever | 14/136 (10.3%) | 18 | 15/139 (10.8%) | 22 |
| Edema limbs | 11/136 (8.1%) | 11 | 7/139 (5%) | 8 |
| Non-cardiac chest pain | 4/136 (2.9%) | 4 | 6/139 (4.3%) | 7 |
| Irritability | 0/136 (0%) | 0 | 1/139 (0.7%) | 4 |
| Infusion related reaction | 3/136 (2.2%) | 3 | 0/139 (0%) | 0 |
| Localized edema | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Edema face | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Edema trunk | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Gait distrubance | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Hepatobiliary disorders | ||||
| Other, specify | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Immune system disorders | ||||
| Allergic reaction | 0/136 (0%) | 0 | 1/139 (0.7%) | 2 |
| Allergic reaction | 7/136 (5.1%) | 9 | 6/139 (4.3%) | 6 |
| Autoimmune disorder | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Anaphylaxis | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Infections and infestations | ||||
| Upper respiratory infection | 1/136 (0.7%) | 2 | 1/139 (0.7%) | 1 |
| Sinusitis | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Skin infection | 3/136 (2.2%) | 3 | 1/139 (0.7%) | 1 |
| Breast infection | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Lip infection | 0/136 (0%) | 0 | 1/139 (0.7%) | 2 |
| Otitis media | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Wound infection | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Pharyngitis | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Device related infection | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Eye infection | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Other, specify | 5/136 (3.7%) | 6 | 2/139 (1.4%) | 2 |
| Upper respiratory infection | 12/136 (8.8%) | 16 | 9/139 (6.5%) | 12 |
| Sinusitis | 9/136 (6.6%) | 12 | 7/139 (5%) | 10 |
| Urinary tract infection | 6/136 (4.4%) | 6 | 5/139 (3.6%) | 7 |
| Skin infection | 4/136 (2.9%) | 4 | 1/139 (0.7%) | 1 |
| Breast infection | 2/136 (1.5%) | 2 | 3/139 (2.2%) | 3 |
| Skin infection | 3/136 (2.2%) | 3 | 2/139 (1.4%) | 2 |
| Vaginal infection | 2/136 (1.5%) | 3 | 2/139 (1.4%) | 2 |
| Lip infection | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Bronchial infection | 3/136 (2.2%) | 4 | 1/139 (0.7%) | 1 |
| Otitis media | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Wound infection | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Pharyngitis | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Papulopustular rash | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Nail infection | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Mucosal infection | 1/136 (0.7%) | 2 | 0/139 (0%) | 0 |
| Laryngitis | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Device related infection | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Bladder infection | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Tooth infection | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Paronychia | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Lung infection | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Anorectal infection | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Other, specify | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Bruising | 10/136 (7.4%) | 12 | 10/139 (7.2%) | 14 |
| Fracture | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Seroma | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Burn | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Other, specify | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Bruising | 1/136 (0.7%) | 2 | 3/139 (2.2%) | 3 |
| Fracture | 3/136 (2.2%) | 3 | 2/139 (1.4%) | 2 |
| Fall | 4/136 (2.9%) | 5 | 0/139 (0%) | 0 |
| Seroma | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Spinal fracture | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Dermatitis radiation | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Burn | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Wrist fracture | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Wound dehiscence | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Radiation recall reaction | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Investigations | ||||
| White blood cell decreased | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Other, specify | 2/136 (1.5%) | 2 | 2/139 (1.4%) | 2 |
| White blood cell decreased | 1/136 (0.7%) | 2 | 6/139 (4.3%) | 8 |
| Ejection fraction decreased | 4/136 (2.9%) | 4 | 5/139 (3.6%) | 5 |
| Creatinine increased | 1/136 (0.7%) | 1 | 4/139 (2.9%) | 5 |
| Alanine aminotransferase increased | 2/136 (1.5%) | 3 | 3/139 (2.2%) | 3 |
| Weight gain | 1/136 (0.7%) | 1 | 4/139 (2.9%) | 4 |
| Neutrophil count decreased | 0/136 (0%) | 0 | 4/139 (2.9%) | 5 |
| Aspartate aminotransferase increased | 3/136 (2.2%) | 3 | 1/139 (0.7%) | 1 |
| Lymphocyte count decreased | 0/136 (0%) | 0 | 3/139 (2.2%) | 3 |
| Alkaline phosphatase increased | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Platelet count decreased | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Weight loss | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Chloesterol high | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Activated partial thromboplastin time prolonged | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Metabolism and nutrition disorders | ||||
| Hyperglycemia | 3/136 (2.2%) | 12 | 5/139 (3.6%) | 6 |
| Anorexia | 3/136 (2.2%) | 3 | 3/139 (2.2%) | 3 |
| Hypokalemia | 3/136 (2.2%) | 3 | 0/139 (0%) | 0 |
| Dehydration | 2/136 (1.5%) | 3 | 0/139 (0%) | 0 |
| Hyponatremia | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Hypocalcemia | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Hyperkalemia | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Hypercalcemia | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/136 (1.5%) | 2 | 3/139 (2.2%) | 3 |
| Myalgia | 3/136 (2.2%) | 5 | 8/139 (5.8%) | 12 |
| Other, specify | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Back pain | 2/136 (1.5%) | 7 | 2/139 (1.4%) | 10 |
| Bone pain | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Pain in extremity | 4/136 (2.9%) | 4 | 6/139 (4.3%) | 11 |
| Neck pain | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Arthralgia | 53/136 (39%) | 103 | 41/139 (29.5%) | 78 |
| Myalgia | 48/136 (35.3%) | 91 | 39/139 (28.1%) | 74 |
| Other, specify | 3/136 (2.2%) | 4 | 2/139 (1.4%) | 2 |
| Back pain | 38/136 (27.9%) | 85 | 39/139 (28.1%) | 58 |
| Bone pain | 22/136 (16.2%) | 47 | 21/139 (15.1%) | 47 |
| Pain in extremity | 12/136 (8.8%) | 15 | 13/139 (9.4%) | 16 |
| Fracture | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Osteoporosis | 2/136 (1.5%) | 2 | 3/139 (2.2%) | 5 |
| Chest wall pain | 0/136 (0%) | 0 | 4/139 (2.9%) | 4 |
| Neck pain | 3/136 (2.2%) | 3 | 0/139 (0%) | 0 |
| Generalized muscle weakness | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Arthritis | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Superficial soft tissue fibrosis | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Osteonecrosis of jaw | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Myositis | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Muscle weakness lower limb | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Exostosis | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Other, specify | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 2 |
| Nervous system disorders | ||||
| Headache | 5/136 (3.7%) | 5 | 4/139 (2.9%) | 12 |
| Neuropathy | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Peripheral sensory neuropathy | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Dysgeusia | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Paresthesia | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Headache | 57/136 (41.9%) | 158 | 57/139 (41%) | 146 |
| Other, specify | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Dizziness | 13/136 (9.6%) | 15 | 17/139 (12.2%) | 25 |
| Neuropathy | 3/136 (2.2%) | 6 | 5/139 (3.6%) | 8 |
| Peripheral sensory neuropathy | 7/136 (5.1%) | 8 | 8/139 (5.8%) | 8 |
| Dysguesia | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 3 |
| Neuralgia | 3/136 (2.2%) | 3 | 2/139 (1.4%) | 2 |
| Lethargy | 0/136 (0%) | 0 | 2/139 (1.4%) | 5 |
| Syncope | 2/136 (1.5%) | 2 | 2/139 (1.4%) | 2 |
| Peripheral motor neuropathy | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 2 |
| Concentration impairment | 0/136 (0%) | 0 | 1/139 (0.7%) | 2 |
| Vasovagal reactions | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Trigeminal nerve disorder | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Somnolence | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Seizure | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Radiculitis | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Presyncope | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Paresthesia | 0/136 (0%) | 0 | 4/139 (2.9%) | 5 |
| Memory impairment | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Edema cerebral | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Depressed level of consciousness | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Psychiatric disorders | ||||
| Anxiety | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Other, specify | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Insomnia | 11/136 (8.1%) | 13 | 11/139 (7.9%) | 11 |
| Anxiety | 4/136 (2.9%) | 5 | 8/139 (5.8%) | 8 |
| Depression | 7/136 (5.1%) | 7 | 5/139 (3.6%) | 5 |
| Agitation | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Personality change | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Libido decreased | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Confusion | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Renal and urinary disorders | ||||
| Urinary tract infection | 1/136 (0.7%) | 1 | 3/139 (2.2%) | 9 |
| Cystitis noninfective | 2/136 (1.5%) | 3 | 1/139 (0.7%) | 1 |
| Urinary incontinence | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Urinary frequency | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Urinary urgency | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Hematuria | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Urinary tract pain | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Renal calculi | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Other, specify | 1/136 (0.7%) | 3 | 3/139 (2.2%) | 3 |
| Breast pain | 5/136 (3.7%) | 6 | 2/139 (1.4%) | 2 |
| Vaginal dryness | 5/136 (3.7%) | 6 | 1/139 (0.7%) | 1 |
| Vaginal hemorrhage | 1/136 (0.7%) | 3 | 0/139 (0%) | 0 |
| Vaginal discharge | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Pelvic pain | 1/136 (0.7%) | 1 | 1/139 (0.7%) | 1 |
| Vaginal inflammation | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Dyspareunia | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Allergic rhinitis | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Dyspnea | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Nasal congestion | 2/136 (1.5%) | 2 | 3/139 (2.2%) | 5 |
| Cough | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Sore throat | 2/136 (1.5%) | 2 | 2/139 (1.4%) | 2 |
| Epistaxis | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Breast pain | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Other, specify | 4/136 (2.9%) | 4 | 4/139 (2.9%) | 4 |
| Allergic Rhinitis | 14/136 (10.3%) | 19 | 14/139 (10.1%) | 19 |
| Dyspnea | 15/136 (11%) | 15 | 18/139 (12.9%) | 21 |
| Nasal congestion | 11/136 (8.1%) | 13 | 12/139 (8.6%) | 13 |
| Cough | 12/136 (8.8%) | 13 | 15/139 (10.8%) | 16 |
| Sore throat | 2/136 (1.5%) | 2 | 5/139 (3.6%) | 8 |
| Epistaxis | 5/136 (3.7%) | 6 | 4/139 (2.9%) | 5 |
| Laryngeal inflammation | 3/136 (2.2%) | 3 | 0/139 (0%) | 0 |
| Sleep apnea | 0/136 (0%) | 0 | 2/139 (1.4%) | 2 |
| Postnasal drip | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Sinus disorder | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Pneumonitis | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Pleuritic pain | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Laryngeal obstruction | 3/136 (2.2%) | 3 | 0/139 (0%) | 0 |
| Hypoxia | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Bronchospasm | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 95/136 (69.9%) | 429 | 89/139 (64%) | 371 |
| Skin induration | 81/136 (59.6%) | 337 | 67/139 (48.2%) | 244 |
| Other, specify | 9/136 (6.6%) | 13 | 10/139 (7.2%) | 21 |
| Rash maculo-papular | 1/136 (0.7%) | 1 | 3/139 (2.2%) | 11 |
| Rash acneiform | 0/136 (0%) | 0 | 1/139 (0.7%) | 4 |
| Nail loss | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Bullous dermatitis | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Pruritus | 5/136 (3.7%) | 5 | 10/139 (7.2%) | 12 |
| Other, specify | 14/136 (10.3%) | 17 | 10/139 (7.2%) | 12 |
| Rash maculo-papular | 6/136 (4.4%) | 6 | 2/139 (1.4%) | 7 |
| Rash acneiform | 6/136 (4.4%) | 9 | 4/139 (2.9%) | 4 |
| Urticaria | 5/136 (3.7%) | 6 | 2/139 (1.4%) | 5 |
| Dry skin | 2/136 (1.5%) | 2 | 2/139 (1.4%) | 3 |
| Nail loss | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Alopecia | 1/136 (0.7%) | 1 | 3/139 (2.2%) | 3 |
| Nail ridging | 1/136 (0.7%) | 1 | 2/139 (1.4%) | 2 |
| Skin hyperpigmentation | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Nail discoloration | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Eythema multiforme | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Surgical and medical procedures | ||||
| Other, specify | 4/136 (2.9%) | 4 | 2/139 (1.4%) | 2 |
| Other, specify | 4/136 (2.9%) | 5 | 4/139 (2.9%) | 4 |
| Vascular disorders | ||||
| Hot flashes | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Lymphedema | 0/136 (0%) | 0 | 1/139 (0.7%) | 1 |
| Hematoma | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Hot flashes | 16/136 (11.8%) | 21 | 18/139 (12.9%) | 21 |
| Lymphedema | 9/136 (6.6%) | 10 | 7/139 (5%) | 7 |
| Hypertension | 7/136 (5.1%) | 8 | 7/139 (5%) | 7 |
| Thromboembolic event | 2/136 (1.5%) | 2 | 2/139 (1.4%) | 2 |
| Hematoma | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Flushing | 2/136 (1.5%) | 2 | 1/139 (0.7%) | 1 |
| Superficial thrombophlebitis | 2/136 (1.5%) | 2 | 0/139 (0%) | 0 |
| Peripheral ischemia | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
| Hypotension | 1/136 (0.7%) | 1 | 0/139 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In the event a Study is a multi-center clinical study, Institution and Principal Investigator will refrain from any disclosure or publication of Study data until the earlier of: (i) the publication of a multi-center publication or (ii) eighteen months following the conclusion of the Study. Nothing in this Article 6 is intended to limit or restrict in any way Sponsor's right to publish independently any Study results.
Results Point of Contact
| Name/Title | Program Director, Karen Arrington, RN, BSN |
|---|---|
| Organization | Cancer Insight |
| Phone | 210-243-5711 |
| karrington@cancerinsight.com |
- 368255
- 1137008 / 20130058