Trial Outcomes & Findings for Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Patients With Locally Recurrent or Metastatic Breast Cancer (NCT NCT00266110)

Last Updated: 2018-09-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

5-6 years

Results posted on

2018-09-12

Participant Flow

Participants were recruited from University of North Carolina (UNC) at Chapel Hill.

105 patients were consented for this study, 103 were on-study, and 17 began treatment.

Participant milestones

Participant milestones
Measure	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 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.
Overall Study STARTED	17
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dendritic Cell Vaccine n=17 Participants 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.
Age, Continuous	65.18 years n=93 Participants
Sex: Female, Male Female	17 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	16 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	17 Participants n=93 Participants

PRIMARY outcome

Timeframe: 5-6 years

Outcome measures

Outcome measures
Measure	Dendritic Cell Vaccine n=17 Participants 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.
Number of Participants With Response	0 Participants

SECONDARY outcome

Timeframe: 13 weeks

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

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

Outcome measures

Outcome measures
Measure	Dendritic Cell Vaccine n=16 Participants 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.
Generation of E75/E90 Tetramer-positive CD8+ T Cells	3.63 Percentage Interval 0.17 to 19.4

SECONDARY outcome

Timeframe: 13 weeks

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

Outcome measures

Outcome measures
Measure	Dendritic Cell Vaccine n=13 Participants 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.
Generation of Interferon Gamma Positive CD8+T Cells	15.99 percentage of cells Interval 0.93 to 36.7

Adverse Events

Dendritic Cell Vaccine

Serious events: 2 serious events

Other events: 12 other events

Deaths: 15 deaths

Serious adverse events

Serious adverse events
Measure	Dendritic Cell Vaccine n=17 participants at risk 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.
Gastrointestinal disorders Nausea	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Gastrointestinal disorders Pain - Abdomen NOS	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Gastrointestinal disorders Constipation	5.9% 1/17 • Toxicity was assessed for 16 weeks.

Other adverse events

Other adverse events
Measure	Dendritic Cell Vaccine n=17 participants at risk 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.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Metabolism and nutrition disorders Anorexia	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Investigations AST, SGOT(serum glutamic oxaloacetic transaminase)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	17.6% 3/17 • Toxicity was assessed for 16 weeks.
Investigations Creatinine	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Gastrointestinal disorders Diarrhea	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	11.8% 2/17 • Toxicity was assessed for 16 weeks.
General disorders Fatigue (asthenia, lethargy, malaise)	35.3% 6/17 • Toxicity was assessed for 16 weeks.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	11.8% 2/17 • Toxicity was assessed for 16 weeks.
Gastrointestinal disorders Heartburn/dyspepsia	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Blood and lymphatic system disorders Hemoglobin	29.4% 5/17 • Toxicity was assessed for 16 weeks.
Vascular disorders Hypotension	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Abdomen NOS	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS	5.9% 1/17 • Toxicity was assessed for 16 weeks.
General disorders Injection site reaction/extravasation changes	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Psychiatric disorders Insomnia	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Investigations Leukocytes (total WBC)	23.5% 4/17 • Toxicity was assessed for 16 weeks.
Metabolism and nutrition disorders Magnesium, serum-high (hypermagnesemia)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	11.8% 2/17 • Toxicity was assessed for 16 weeks.
Psychiatric disorders Mood alteration - Anxiety	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Nervous system disorders Neuropathy: sensory	11.8% 2/17 • Toxicity was assessed for 16 weeks.
Investigations Neutrophils/granulocytes (ANC/AGC)	17.6% 3/17 • Toxicity was assessed for 16 weeks.
Gastrointestinal disorders Pain - Abdomen NOS	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Musculoskeletal and connective tissue disorders Pain - Back	11.8% 2/17 • Toxicity was assessed for 16 weeks.
Musculoskeletal and connective tissue disorders Pain - Bone	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Musculoskeletal and connective tissue disorders Pain - Extremity-limb	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Musculoskeletal and connective tissue disorders Pain - Muscle	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Musculoskeletal and connective tissue disorders Pain - Neck	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Investigations Platelets	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	23.5% 4/17 • Toxicity was assessed for 16 weeks.
General disorders Rigors/chills	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	23.5% 4/17 • Toxicity was assessed for 16 weeks.
Nervous system disorders Speech impairment (e.g., dysphasia or aphasia)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Nervous system disorders Taste alteration (dysgeusia)	5.9% 1/17 • Toxicity was assessed for 16 weeks.
Skin and subcutaneous tissue disorders Urticaria (hives, welts, wheals)	11.8% 2/17 • Toxicity was assessed for 16 weeks.
Investigations Weight loss	5.9% 1/17 • Toxicity was assessed for 16 weeks.

Additional Information

Robin V. Johnson

UNC Lineberger Comprehensive Cancer Center

Phone: 919-966-1125

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place