Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00971737
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 63
• Location: 1
• Arms: 2
• Duration (Months): 80
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and trastuzumab, may increase the number of immune cells and make the immune response stronger. It is not yet known whether giving cyclophosphamide together with vaccine therapy is more effective with or without trastuzumab in treating patients with metastatic breast cancer.

PURPOSE: This randomized phase II trial is studying the side effects of giving cyclophosphamide together with vaccine therapy and to see how well it works compared with giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients with metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: allogeneic GM-CSF-secreting breast cancer vaccine; Biological: trastuzumab; Drug: cyclophosphamide	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To evaluate the safety of cyclophosphamide-modulated vaccination with vs without trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.

• To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs without trastuzumab in these patients.

• To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type hypersensitivity (DTH) and ELISPOT.

• To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.

Secondary

• To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry of vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms, comparing cellular infiltrates to those seen in previous preclinical and clinical models.

• To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.

• To characterize the peripheral-memory T-cell pool.

Tertiary

• To determine baseline and change in vaccine site-draining lymph node immunohistology and gene expression profile.

• To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T cells.

• To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.

• Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.

Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of courses 1 and 3 for biomarker analysis.

After completion of study treatment, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label Comparative Study of Combination Therapy With Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine With or Without Trastuzumab for the Treatment of Metastatic Breast Cancer That Does NOT Over-express HER-2/Neu
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cyclophosphamide and Vaccine only Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.	Biological: allogeneic GM-CSF-secreting breast cancer vaccine; Given intradermally; Drug: cyclophosphamide; Given IV
Experimental: Cyclophosphamide, Vaccine and Trastuzumab Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.	Biological: allogeneic GM-CSF-secreting breast cancer vaccine; Given intradermally; Biological: trastuzumab; Given IV; Drug: cyclophosphamide; Given IV

Outcome Measures

Primary Outcome Measures

1. Toxicity as Assessed by Number of Grade 3 or 4 Adverse Events [3 years]

   Number of grade 3 or 4 nonhematologic toxicity (except alopecia), or any grade 4 hematologic toxicity as defined by NCI CTCAE v3.0

2. Clinical Benefit (CB) as Assessed by Progression Free Survival at Six Months [6 months post-intervention]

   Progression-free survival is measured as percentage of participants with stable disease or complete response, as defined by RECIST criteria, six months after receiving last vaccination. Progressive disease (PD) will be defined by the appearance of a new lesion, or by an increase of at least 20% in the sum of the longest diameter of target lesions, taking as a reference that smallest sum longest diameter recorded since the study intervention began. In the case of bone lesions, progressive disease will be established after eight weeks of increasing or new lesions if there is subjective progressive disease as noted by increasing bone pain or decreasing performance status. These observations must be present for at least two measurement periods separated by at least four weeks.

3. HER-2/Neu-specific Immune Responses as Measured by Number of Participants With Positive for Delayed-type Hypersensitivity (DTH) Response [3 years]

4. Pharmacodynamics of Peripheral CD4+CD25+ Regulatory T Cells [3 years]

Secondary Outcome Measures

1. Immune Priming in In-vivo Vaccine-site Biopsies [3 years]

2. Enumeration of CD8+ T Cells Specific for hTERT by ELISPOT [3 years]

3. Characterization of the T-cell Memory Pool Pre- and Post-vaccination [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

• Does not overexpress HER-2/neu, defined as FISH negative or 0, 1+, or 2+ by IHC

• Stage IV disease

• Must not be eligible for therapy of known curative potential for metastatic breast cancer

• Measurable or evaluable disease

• Stable CNS disease allowed provided that it's adequately treated and not under active treatment

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• ECOG performance status 0-1

• ANC > 1,000/mm^3

• Platelets > 100,000/mm^3

• Serum bilirubin < 2.0 mg/dL (unless due to Gilbert syndrome)

• AST and ALT < 2 times upper limit of normal (ULN)

• Alkaline phosphatase < 5 times ULN

• Serum creatinine < 2.0 mg/dL

• Ejection fraction normal by MUGA OR ≥ 50% by echocardiogram

• Not pregnant or nursing

• Fertile patients must use effective contraception

• HIV negative

• Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed

• No prior or concurrent autoimmune disease requiring management with systemic immunosuppression, including any of the following:

• Inflammatory bowel disease

• Systemic vasculitis

• Scleroderma

• Psoriasis

• Multiple sclerosis

• Hemolytic anemia or immune-mediated thrombocytopenia

• Rheumatoid arthritis

• Systemic lupus erythematosus

• Sjogren syndrome

• Sarcoidosis

• Other rheumatologic disease

• No other malignancies within the past 5 years, except carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, superficial bladder cancer, or tamoxifen-related endometrial cancer that has been adequately treated

• No active major medical or psychosocial problems that could be complicated by study participation

• No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest

• No uncontrolled medical problems

• No evidence of active acute or chronic infection

• No known severe hypersensitivity to trastuzumab, except mild to moderate infusion reactions that are easily managed and do not recur

• No allergy to corn

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 28 days since prior and no other concurrent chemotherapy, radiation therapy, or biologic therapy (except trastuzumab)

• Concurrent endocrine therapy and supportive therapy with bisphosphonates allowed

• More than 28 days since prior and no other concurrent participation in an investigational new drug trial

• More than 28 days since prior and no other concurrent systemic oral steroids

• Topical, ocular, and nasal steroids allowed

• No prior vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Leisha A. Emens, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00971737
• Other Study ID Numbers: J0947; P30CA006973; JHOC-J0947; NA_00024527; GENENTECH-JHOC-J0947; CDR0000653173
• First Posted: Sep 4, 2009
• Last Update Posted: Apr 24, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: stage IV breast cancer; male breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Cyclophosphamide; Trastuzumab

Study Results

Participant Flow

Pre-assignment Detail	3 subjects were withdrawn prior to receiving intervention (2 due to development of new medical problems, 1 due to anxiety and non-compliance).

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Period Title: Overall Study
STARTED	30	30
COMPLETED	30	30
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab	Total
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV	Total of all reporting groups
Overall Participants	30	30	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	27 90%	25 83.3%	52 86.7%
>=65 years	3 10%	5 16.7%	8 13.3%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53	52	53
Sex: Female, Male (Count of Participants)
Female	30 100%	30 100%	60 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%	30 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Toxicity as Assessed by Number of Grade 3 or 4 Adverse Events
Description	Number of grade 3 or 4 nonhematologic toxicity (except alopecia), or any grade 4 hematologic toxicity as defined by NCI CTCAE v3.0
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Data was not evaluable in 2/30 participants from the cyclophosphamide and vaccine-only arm.

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Measure Participants	28	30
Number [adverse events]	0	2

2. Primary Outcome

Title	Clinical Benefit (CB) as Assessed by Progression Free Survival at Six Months
Description	Progression-free survival is measured as percentage of participants with stable disease or complete response, as defined by RECIST criteria, six months after receiving last vaccination. Progressive disease (PD) will be defined by the appearance of a new lesion, or by an increase of at least 20% in the sum of the longest diameter of target lesions, taking as a reference that smallest sum longest diameter recorded since the study intervention began. In the case of bone lesions, progressive disease will be established after eight weeks of increasing or new lesions if there is subjective progressive disease as noted by increasing bone pain or decreasing performance status. These observations must be present for at least two measurement periods separated by at least four weeks.
Time Frame	6 months post-intervention

Outcome Measure Data

Analysis Population Description

Data was not evaluable in 2/30 participants from the cyclophosphamide and vaccine-only arm.

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Measure Participants	28	30
Number (95% Confidence Interval) [percentage of participants]	33 110%	37 123.3%

3. Primary Outcome

Title	HER-2/Neu-specific Immune Responses as Measured by Number of Participants With Positive for Delayed-type Hypersensitivity (DTH) Response
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Data was not evaluable in 2/30 participants from the cyclophosphamide and vaccine-only arm.

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Measure Participants	28	30
Count of Participants [Participants]	14 46.7%	16 53.3%

4. Primary Outcome

Title	Pharmacodynamics of Peripheral CD4+CD25+ Regulatory T Cells
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Lab analysis could not be completed due to loss of funding, therefore data was not collected to assess this outcome measure.

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Measure Participants	0	0

5. Secondary Outcome

Title	Immune Priming in In-vivo Vaccine-site Biopsies
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Lab analysis could not be completed due to loss of funding, therefore data was not collected to assess this outcome measure

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Measure Participants	0	0

6. Secondary Outcome

Title	Enumeration of CD8+ T Cells Specific for hTERT by ELISPOT
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Lab analysis could not be completed due to loss of funding, therefore data was not collected to assess this outcome measure.

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Measure Participants	0	0

7. Secondary Outcome

Title	Characterization of the T-cell Memory Pool Pre- and Post-vaccination
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Lab analysis could not be completed due to loss of funding, therefore data was not collected to assess this outcome measure.

Arm/Group Title	Cyclophosphamide and Vaccine Only	Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV	Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
Measure Participants	0	0

Adverse Events

Time Frame	up to 6 months post-intervention
Arm/Group Title	Cyclophosphamide and Vaccine Only		Cyclophosphamide, Vaccine and Trastuzumab
Arm/Group Description	Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally cyclophosphamide: Given IV		Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months. allogeneic GM-CSF-secreting breast cancer vaccine: Given intradermally trastuzumab: Given IV cyclophosphamide: Given IV
All Cause Mortality
	Cyclophosphamide and Vaccine Only		Cyclophosphamide, Vaccine and Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Cyclophosphamide and Vaccine Only		Cyclophosphamide, Vaccine and Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Cyclophosphamide and Vaccine Only		Cyclophosphamide, Vaccine and Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/30 (100%)		30/30 (100%)
Blood and lymphatic system disorders
Lymphadenopathy	9/30 (30%)	14	19/30 (63.3%)	31
Cardiac disorders
Hypotension	0/30 (0%)	0	1/30 (3.3%)	1
Gastrointestinal disorders
Anorexia	13/30 (43.3%)	22	10/30 (33.3%)	17
Aphthus Ulcers	0/30 (0%)	0	1/30 (3.3%)	2
Constipation	1/30 (3.3%)	1	1/30 (3.3%)	1
Diarrhea	1/30 (3.3%)	1	0/30 (0%)	0
Dry throat	0/30 (0%)	0	1/30 (3.3%)	1
Flatulence	0/30 (0%)	0	1/30 (3.3%)	1
Indigestion	0/30 (0%)	0	1/30 (3.3%)	1
Mucositis	0/30 (0%)	0	1/30 (3.3%)	1
Nausea	12/30 (40%)	16	8/30 (26.7%)	10
Vomiting	2/30 (6.7%)	3	2/30 (6.7%)	3
General disorders
Chills	16/30 (53.3%)	29	15/30 (50%)	27
Fatigue	16/30 (53.3%)	34	18/30 (60%)	32
Fever	11/30 (36.7%)	18	11/30 (36.7%)	17
Flu-like symptoms	2/30 (6.7%)	2	2/30 (6.7%)	3
Malaise	2/30 (6.7%)	2	3/30 (10%)	4
Sweats	0/30 (0%)	0	1/30 (3.3%)	1
Infections and infestations
Infection, Herpes	0/30 (0%)	0	1/30 (3.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	15/30 (50%)	32	19/30 (63.3%)	33
Myalgia	16/30 (53.3%)	41	22/30 (73.3%)	37
Neck stiffness	1/30 (3.3%)	3	0/30 (0%)	0
Pain, bone	0/30 (0%)	0	1/30 (3.3%)	2
Pain, hip/groin	0/30 (0%)	0	1/30 (3.3%)	1
Nervous system disorders
Dizziness	1/30 (3.3%)	1	1/30 (3.3%)	1
Headache	11/30 (36.7%)	21	15/30 (50%)	18
Psychiatric disorders
Insomnia	2/30 (6.7%)	5	6/30 (20%)	8
Skin and subcutaneous tissue disorders
Erythema/swelling of vaccine sites	30/30 (100%)	82	30/30 (100%)	102
Pain/soreness/tenderness of vaccine sites	28/30 (93.3%)	81	30/30 (100%)	82
Pruritus of vaccine sites	30/30 (100%)	78	30/30 (100%)	92
Rash around vaccine sites	2/30 (6.7%)	3	3/30 (10%)	3
Blister at vaccine site	16/30 (53.3%)	28	20/30 (66.7%)	41
Ecchymosis at vaccine site	8/30 (26.7%)	10	18/30 (60%)	24
Hyperpigmentation at vaccine site	1/30 (3.3%)	1	3/30 (10%)	3
Warmth at vaccine site	16/30 (53.3%)	26	17/30 (56.7%)	34
Bruising	0/30 (0%)	0	1/30 (3.3%)	1
Dermatographism	0/30 (0%)	0	1/30 (3.3%)	1
Eczema	1/30 (3.3%)	1	1/30 (3.3%)	1
Erythema	3/30 (10%)	5	2/30 (6.7%)	3
Pruritis	2/30 (6.7%)	2	3/30 (10%)	4
Rash	7/30 (23.3%)	10	9/30 (30%)	12
Urticaria	3/30 (10%)	4	5/30 (16.7%)	5
Vaccine flare	2/30 (6.7%)	2	1/30 (3.3%)	1
Hives	2/30 (6.7%)	9	5/30 (16.7%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.