Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT00266110
• Recruitment Status: Completed
• First Posted: December 15, 2005
• Results First Posted: May 9, 2017
• Last Update Posted: September 12, 2018
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); Susan G. Komen Breast Cancer Foundation
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer
• Interventions: Biological: sargramostim; Biological: therapeutic autologous dendritic cells; Biological: trastuzumab; Drug: vinorelbine ditartrate
• Enrollment: 17

Participant Flow

Recruitment Details	Participants were recruited from University of North Carolina (UNC) at Chapel Hill.
Pre-assignment Details	105 patients were consented for this study, 103 were on-study, and 17 began treatment.

Arm/Group Title	Dendritic Cell Vaccine
Arm/Group Description	Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion Sargramostim: All patients will receive Leukine (GM-CSF) at 250 mcg/m2 starting one day after the administration of chemotherapy x 7 days. Patients with neutrophil counts below 1,000/mm3 on day 8 will continue GM-CSF therapy until the neutrophil count is greater than 1,000/mm3. Therapeutic autologous dendritic cells: patients will receive (10 x 106) peptide-pulsed dendritic cells (DCs) given by i.d injection into either axilla or the inguinal region with each peptide given into a separate site. The total dose will be 20 x 106 DCs given per treatment. Trastuzumab: Trastuzumab will be infused in the side-port of a freely flowing IV over 90 minutes and at 6mg/kg if the subject has not previously received Trastuzumab, or if it has been more than 30 days since any prior trastuzumab administration.
Period Title: Overall Study
Started	17
Completed	10
Not Completed	7

Baseline Characteristics

Arm/Group Title		Dendritic Cell Vaccine
Arm/Group Description		Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion sargramostim: All patients will receive Leukine (GM-CSF) at 250 mcg/m2 starting one day after the administration of chemotherapy x 7 days. Patients with neutrophil counts below 1,000/mm3 on day 8 will continue GM-CSF therapy until the neutrophil count is greater than 1,000/mm3. therapeutic autologous dendritic cells: patients will receive (10 x 106) peptide-pulsed DCs given by i.d injection into either axilla or the inguinal region with each peptide given into a separate site. The total dose will be 20 x 106 DCs given per treatment. trastuzumab: Trastuzumab will be infused in the side-port of a freely flowing IV over 90 minutes and at 6mg/kg if the subject has not previously received Trastuzumab, or if it has been more than 30 days since any prior trastuzumab administration.
Overall Number of Baseline Participants		17
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	17 participants
		65.18; (47 to 80)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants
	Female	17 100.0%
	Male	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	17 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	1 5.9%
	White	16 94.1%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	17 participants
		17 100.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Response
Description	Response: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	5-6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dendritic Cell Vaccine
Arm/Group Description:	Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion sargramostim: All patients will receive Leukine (GM-CSF) at 250 mcg/m2 starting one day after the administration of chemotherapy x 7 days. Patients with neutrophil counts below 1,000/mm3 on day 8 will continue GM-CSF therapy until the neutrophil count is greater than 1,000/mm3. therapeutic autologous dendritic cells: patients will receive (10 x 106) peptide-pulsed DCs given by i.d injection into either axilla or the inguinal region with each peptide given into a separate site. The total dose will be 20 x 106 DCs given per treatment. trastuzumab: Trastuzumab will be infused in the side-port of a freely flowing IV over 90 minutes and at 6mg/kg if the subject has not previously received Trastuzumab, or if it has been more than 30 days since any prior trastuzumab administration.
Overall Number of Participants Analyzed	17
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

2. Secondary Outcome

Title	Generation of E75/E90 Tetramer-positive CD8+ T Cells
Description	Evaluate the ability of peptide-pulsed dendritic cells plus trastuzumab to induce functional antigen specific T cells. Measured by percentage of intracellular cytokine staining for E75/E90 tetramer-positive CD8+ T cells
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

One patient failed to have blood drawn for correlative studies following second vaccine.

Arm/Group Title	Dendritic Cell Vaccine
Arm/Group Description:	Experimental: Dendritic Cell Vaccine Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion
Overall Number of Participants Analyzed	16
Mean (Full Range); Unit of Measure: Percentage
	3.63; (.17 to 19.4)

3. Secondary Outcome

Title	Generation of Interferon Gamma Positive CD8+T Cells
Description	Evaluate the ability of peptide-pulsed dendritic cells plus trastuzumab to induce functional antigen specific T cells. Measured by percentage of intracellular cytokine staining for interferon gamma positive CD8+ T cells
Time Frame	13 weeks

Outcome Measure Data

Analysis Population Description

Three subjects had insufficient samples due to early withdraw from study, and one subject was removed from study before the vaccine was administered.

Arm/Group Title	Dendritic Cell Vaccine
Arm/Group Description:	Experimental: Dendritic Cell Vaccine Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion
Overall Number of Participants Analyzed	13
Mean (Full Range); Unit of Measure: percentage of cells
	15.99; (0.93 to 36.7)

Adverse Events

Time Frame	Toxicity was assessed for 16 weeks.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Dendritic Cell Vaccine
Arm/Group Description	Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion sargramostim: All patients will receive Leukine (GM-CSF) at 250 mcg/m2 starting one day after the administration of chemotherapy x 7 days. Patients with neutrophil counts below 1,000/mm3 on day 8 will continue GM-CSF therapy until the neutrophil count is greater than 1,000/mm3. therapeutic autologous dendritic cells: patients will receive (10 x 106) peptide-pulsed DCs given by i.d injection into either axilla or the inguinal region with each peptide given into a separate site. The total dose will be 20 x 106 DCs given per treatment. trastuzumab: Trastuzumab will be infused in the side-port of a freely flowing IV over 90 minutes and at 6mg/kg if the subject has not previously received Trastuzumab, or if it has been more than 30 days since any prior trastuzumab administration.
All-Cause Mortality
	Dendritic Cell Vaccine
	Affected / at Risk (%)
Total	15/17 (88.24%)
Serious Adverse Events
	Dendritic Cell Vaccine
	Affected / at Risk (%)
Total	2/17 (11.76%)
Gastrointestinal disorders
Nausea * 1	1/17 (5.88%)
Pain - Abdomen NOS * 1	1/17 (5.88%)
Constipation * 1	1/17 (5.88%)
1 Term from vocabulary, CTCAE (3.0); * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Dendritic Cell Vaccine
	Affected / at Risk (%)
Total	12/17 (70.59%)
Blood and lymphatic system disorders
Hemoglobin * 1	5/17 (29.41%)
Gastrointestinal disorders
Diarrhea * 1	1/17 (5.88%)
Heartburn/dyspepsia * 1	1/17 (5.88%)
Pain - Abdomen NOS * 1	1/17 (5.88%)
General disorders
Fatigue (asthenia, lethargy, malaise) * 1	6/17 (35.29%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) * 1	1/17 (5.88%)
Injection site reaction/extravasation changes * 1	1/17 (5.88%)
Rigors/chills * 1	1/17 (5.88%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Abdomen NOS * 1	1/17 (5.88%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS * 1	1/17 (5.88%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase) * 1	1/17 (5.88%)
AST, SGOT(serum glutamic oxaloacetic transaminase) * 1	1/17 (5.88%)
Creatinine * 1	1/17 (5.88%)
Leukocytes (total WBC) * 1	4/17 (23.53%)
Neutrophils/granulocytes (ANC/AGC) * 1	3/17 (17.65%)
Platelets * 1	1/17 (5.88%)
Weight loss * 1	1/17 (5.88%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia) * 1	1/17 (5.88%)
Anorexia * 1	1/17 (5.88%)
Calcium, serum-low (hypocalcemia) * 1	3/17 (17.65%)
Glucose, serum-high (hyperglycemia) * 1	2/17 (11.76%)
Magnesium, serum-high (hypermagnesemia) * 1	1/17 (5.88%)
Magnesium, serum-low (hypomagnesemia) * 1	2/17 (11.76%)
Potassium, serum-high (hyperkalemia) * 1	4/17 (23.53%)
Sodium, serum-low (hyponatremia) * 1	4/17 (23.53%)
Musculoskeletal and connective tissue disorders
Pain - Back * 1	2/17 (11.76%)
Pain - Bone * 1	1/17 (5.88%)
Pain - Extremity-limb * 1	1/17 (5.88%)
Pain - Muscle * 1	1/17 (5.88%)
Pain - Neck * 1	1/17 (5.88%)
Nervous system disorders
Neuropathy: sensory * 1	2/17 (11.76%)
Speech impairment (e.g., dysphasia or aphasia) * 1	1/17 (5.88%)
Taste alteration (dysgeusia) * 1	1/17 (5.88%)
Psychiatric disorders
Insomnia * 1	1/17 (5.88%)
Mood alteration - Anxiety * 1	1/17 (5.88%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) * 1	1/17 (5.88%)
Dyspnea (shortness of breath) * 1	2/17 (11.76%)
Skin and subcutaneous tissue disorders
Urticaria (hives, welts, wheals) * 1	2/17 (11.76%)
Vascular disorders
Hypotension * 1	1/17 (5.88%)
1 Term from vocabulary, CTCAE (3.0); * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Robin V. Johnson
• Organization: UNC Lineberger Comprehensive Cancer Center
• Phone: 919-966-1125
• EMail: Robin_V_Johnson@med.unc.edu

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00266110
• Other Study ID Numbers: LCCC 0418; P50CA058223 ( U.S. NIH Grant/Contract ); R21CA105837 ( U.S. NIH Grant/Contract ); KG100307 ( Other Grant/Funding Number: Susan G Komen for the Cure )
• First Submitted: December 13, 2005
• First Posted: December 15, 2005
• Results First Submitted: March 28, 2017
• Results First Posted: May 9, 2017
• Last Update Posted: September 12, 2018