Vaccination With Autologous Breast Cancer Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Metastatic Breast Cancer Patients

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00317603
• Collaborator: Brigham and Women's Hospital (Other)
• Enrollment: 15
• Locations: 2
• Arm: 1
• Actual Duration (Months): 185
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this trial is to test the safety of a vaccine made from a patient's own breast cancer cells, and determine if this vaccine will delay or stop the growth of the cancer. The vaccine is made by genetically modifying a patient's own tumor cells to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) to activate the immune response.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: Autologous, Lethally Irradiated Breast Cancer Cells	Phase 1

Detailed Description

After the patient has given their consent to participate in the trial, a series of tests will be performed to determine if the patient is eligible. These tests may take place up to 21 days before the surgery to remove a tumor sample or cancer-containing fluid, which will be used to create the vaccines. The tumor cells or fluid is then brought to a special, certified laboratory where the vaccine is made. Specially trained laboratory technicians then use a method known as adenoviral mediated gene transfer, which adds a new gene to the cancer cells. This gene causes the cells to make GM-CSF, a powerful hormone that stimulates the immune system. The cells are then given radiation so that they will not grow. Participants will start receiving vaccine on day 1, 8, 15, 29, and then every two weeks until the supply of vaccine has run out. The amount of the vaccine depends upon the total amount of cells that are obtained from the breast cancer tumor or fluid. Each time the patient is vaccinated, they will be given injections that will be placed underneath the skin. A different place will be used for each injection. If there are enough cells from the patient's tumor sample, the patient will be given an injection of non-transduced irradiated cells (the gene was not added) . These cells will help to measure how the patient's immune system is reacting to the tumor cells. This is called Delayed-Type Hypersensitivity (DTH). With vaccine #1 and #5, the patient will also receive a DTH injection. Two to three days after the vaccine and DTH injection, skin biopsies will be taken of both sites. At week 10 in the study treatment, or earlier if necessary, the patient will have a chest, abdomen, and pelvic CT scan to determine if the vaccine therapy has had an effect on their disease. A brain MRI will be performed if there were any abnormalities on the first brain MRI or if new symptoms have developed. Patients may participate in this study until one of the following happens: All vaccine created from the tumor has been given to the patient; the patient's disease worsens; the patient experiences an unacceptable and/or harmful side effect; the patient is unable to follow the study plan; or the patient's doctor feels it is no longer in the best interest of the patient to continue.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Trial of Vaccination With Autologous, Lethally Irradiated Breast Cancer Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete Granulocyte-Macrophage Colony Stimulating Factor in Metastatic Breast Cancer Patients
• Actual Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vaccine Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 , 1x10 6 , or 1x10 5 depending on the final cell yield.	Biological: Autologous, Lethally Irradiated Breast Cancer Cells; Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out

Outcome Measures

Primary Outcome Measures

1. Minimum Number of Vaccine Doses Created Using Participant Tumor Sample [Vaccine doses created and banked soon after registration, up to 8 days.]

   Tumor samples were obtained via malignant effusion or a surgically accessible tumor nodule of 2 cm in greatest diameter. Tumor cells were processed to single cell suspension and transduced with adenoviral vector encoding human Granulocyte-macrophage colony-stimulating factor (GM-CSF). Then, the cells washed extensively and irradiated with 10,000 cGy. Over the next 14 days, sterility cultures were tested for endotoxin and mycoplasma contamination. Individual vaccine cell dose and number varied depending on the final cell yield from vaccine production. The minimal dose was 1 x 10^5 cells and the maximal dose was 1 x 10^7 cells.

Secondary Outcome Measures

1. Number of Participants With Grade 3 or Higher Adverse Events [Up to 58 Months]

   Number of participants with grade 3 or higher adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

2. Number of Participants With RECIST Criteria Responses [Up to 14 Years]

   Clinical outcomes as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed Stage IV breast cancer

• Prior banked malignant effusion or significant malignant effusion for tumor harvest or surgically-accessible tumor nodule of at least 2cm in greatest diameter by physical exam, magnetic resonance imaging (MRI) or computed tomography (CT) scan

• Must have received at least one prior regimen of chemotherapy for metastatic disease

• Patients with HER2 positive tumors must have received at least one prior trastuzumab-based therapy in the metastatic setting, and may not receive trastuzumab therapy and vaccine treatment concurrently

• Patients may receive concurrent bisphosphonate therapy and/or erythropoetin therapy at any point while on study

• ECOG performance status 0 or 1

• Estimated life expectancy of greater than or equal to 6 months

• 18 years of age or older

• Greater than 4 weeks from immunotherapy, or systemic glucocorticoid therapy

• Adequate recovery from drug-related toxicities from prior systemic therapies

• Adequate recovery from recent surgery and radiation therapy

• Greater than 6 months since bone marrow or peripheral blood stem cell transplant

Exclusion Criteria:

• Urgent need for cytotoxic chemotherapy, radiotherapy, or surgery in the next 60 days

• Uncontrolled active infection or illness

• Psychiatric illness/social situation that would limit study compliance

• Pregnant or nursing mothers

• Evidence of HIV infection

• Previous participation in an adenovirus-based trial

• Concurrent invasive malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital

Investigators

• Principal Investigator: Beth Overmoyer, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ana C Garrido-Castro, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00317603
• Other Study ID Numbers: 05-111
• First Posted: Apr 25, 2006
• Last Update Posted: Apr 1, 2022
• Last Verified: Mar 1, 2022

• Keywords provided by Ana C Garrido-Castro, Principal Investigator, Dana-Farber Cancer Institute: autologous vaccination; GM-CSF; adenoviral mediated gene transfer; Stage IV breast cancer
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Recruitment Details	January 2006 through May 2008

Arm/Group Title	Vaccine
Arm/Group Description	Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 , 1x10 6 , or 1x10 5 depending on the final cell yield. Autologous, Lethally Irradiated Breast Cancer Cells: Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
Period Title: Overall Study
STARTED	15
Treated	12
COMPLETED	12
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Vaccine
Arm/Group Description	Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 , 1x10 6 , or 1x10 5 depending on the final cell yield. Autologous, Lethally Irradiated Breast Cancer Cells: Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
Overall Participants	12
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	51.5
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 8.3%
White	11 91.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Site of Disease (Count of Participants)
Skin / Lymph Nodes	9 75%
Pleura	8 66.7%
Bone	9 75%
Viscera	9 75%
Central Nervous System	1 8.3%
Ascites	1 8.3%
Chest Wall	1 8.3%
Median Duration of Stage IV Breast Cancer (years) [Median (Full Range) ]
Median (Full Range) [years]	3.45
Hormone Receptor Status (Count of Participants)
Positive	8 66.7%
Negative	4 33.3%
Human Epidermal Growth Factor Receptor 2 Status (Count of Participants)
Positive	5 41.7%
Negative	7 58.3%
Median number of prior lines of chemotherapy in the metastatic setting (range) (therapies) [Median (Full Range) ]
Median (Full Range) [therapies]	2.5

Outcome Measures

1. Primary Outcome

Title	Minimum Number of Vaccine Doses Created Using Participant Tumor Sample
Description	Tumor samples were obtained via malignant effusion or a surgically accessible tumor nodule of 2 cm in greatest diameter. Tumor cells were processed to single cell suspension and transduced with adenoviral vector encoding human Granulocyte-macrophage colony-stimulating factor (GM-CSF). Then, the cells washed extensively and irradiated with 10,000 cGy. Over the next 14 days, sterility cultures were tested for endotoxin and mycoplasma contamination. Individual vaccine cell dose and number varied depending on the final cell yield from vaccine production. The minimal dose was 1 x 10^5 cells and the maximal dose was 1 x 10^7 cells.
Time Frame	Vaccine doses created and banked soon after registration, up to 8 days.

Outcome Measure Data

Analysis Population Description

Vaccinations prepared for "enrolled for vaccine administration" population.

Arm/Group Title	Vaccine
Arm/Group Description	Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 , 1x10 6 , or 1x10 5 depending on the final cell yield. Autologous, Lethally Irradiated Breast Cancer Cells: Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
Measure Participants	12
Number [doses]	6

2. Secondary Outcome

Title	Number of Participants With Grade 3 or Higher Adverse Events
Description	Number of participants with grade 3 or higher adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame	Up to 58 Months

Outcome Measure Data

Analysis Population Description

Analysis population for adverse events is "Treated" population.

Arm/Group Title	Vaccine
Arm/Group Description	Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 , 1x10 6 , or 1x10 5 depending on the final cell yield. Autologous, Lethally Irradiated Breast Cancer Cells: Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
Measure Participants	12
Grade 3	0 0%
Grade 4	0 0%
Grade 5	0 0%

3. Secondary Outcome

Title	Number of Participants With RECIST Criteria Responses
Description	Clinical outcomes as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.
Time Frame	Up to 14 Years

Outcome Measure Data

Analysis Population Description

Clinical outcomes assessed for the "treated" population.

Arm/Group Title	Vaccine
Arm/Group Description	Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 , 1x10 6 , or 1x10 5 depending on the final cell yield. Autologous, Lethally Irradiated Breast Cancer Cells: Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
Measure Participants	12
Progressive Disease within 2 months	8 66.7%
Stable Disease with progression at 4 months	2 16.7%
Stable Disease with progression at 13 months	1 8.3%
No Evidence of Disease > 12 years	1 8.3%

Adverse Events

Time Frame	14 Years
Adverse Event Reporting Description	Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Arm/Group Title	Vaccine
Arm/Group Description	Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 , 1x10 6 , or 1x10 5 depending on the final cell yield. Autologous, Lethally Irradiated Breast Cancer Cells: Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
All Cause Mortality
	Vaccine
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Serious Adverse Events
	Vaccine
	Affected / at Risk (%)	# Events
Total	3/12 (25%)
Blood and lymphatic system disorders
Hemoglobin	1/12 (8.3%)
Investigations
Alkaline phosphatase	1/12 (8.3%)
Metabolism and nutrition disorders
Dehydration	1/12 (8.3%)
Nervous system disorders
Syncope	2/12 (16.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/12 (8.3%)
Vascular disorders
Hypotension	1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Vaccine
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Hemoglobin	8/12 (66.7%)
Cardiac disorders
Palpitations	1/12 (8.3%)
Ventricular tachycardia	1/12 (8.3%)
Gastrointestinal disorders
Constipation	3/12 (25%)
Diarrhea w/o prior colostomy	4/12 (33.3%)
Distention/bloating, abdominal	1/12 (8.3%)
Gastritis	1/12 (8.3%)
Dyspepsia	1/12 (8.3%)
Nausea	10/12 (83.3%)
Vomiting	7/12 (58.3%)
Lip, pain	8/12 (66.7%)
General disorders
Fatigue	10/12 (83.3%)
Fever w/o neutropenia	4/12 (33.3%)
Rigors/chills	1/12 (8.3%)
Injection site reaction	8/12 (66.7%)
Edema head and neck	1/12 (8.3%)
Edema limb	8/12 (66.7%)
Chest/thoracic pain NOS	1/12 (8.3%)
Pain NOS	1/12 (8.3%)
Infections and infestations
Infection Gr0-2 neut, sinus	1/12 (8.3%)
Injury, poisoning and procedural complications
Bruising	1/12 (8.3%)
Investigations
Leukocytes	6/12 (50%)
Lymphopenia	1/12 (8.3%)
Neutrophils	3/12 (25%)
Platelets	2/12 (16.7%)
Alkaline phosphatase	6/12 (50%)
ALT, SGPT	3/12 (25%)
AST, SGOT	6/12 (50%)
Bilirubin	1/12 (8.3%)
Creatinine	1/12 (8.3%)
Vital capacity	1/12 (8.3%)
Metabolism and nutrition disorders
Anorexia	3/12 (25%)
Hypoalbuminemia	8/12 (66.7%)
Hypercalcemia	3/12 (25%)
Hypocalcemia	4/12 (33.3%)
Hyperglycemia	8/12 (66.7%)
Hypomagnesemia	1/12 (8.3%)
Hypokalemia	3/12 (25%)
Hypernatremia	1/12 (8.3%)
Hyponatremia	6/12 (50%)
Musculoskeletal and connective tissue disorders
Arthritis	1/12 (8.3%)
Lumbar spine-range of motion	1/12 (8.3%)
Back, pain	3/12 (25%)
Bone, pain	1/12 (8.3%)
Extremity-limb, pain	1/12 (8.3%)
Joint, pain	1/12 (8.3%)
Muscle, pain	2/12 (16.7%)
Neck, pain	1/12 (8.3%)
Nervous system disorders
Dizziness	3/12 (25%)
Neuropathy-sensory	2/12 (16.7%)
Tremor	1/12 (8.3%)
Head/headache	4/12 (33.3%)
Psychiatric disorders
Insomnia	4/12 (33.3%)
Renal and urinary disorders
Proteinuria	1/12 (8.3%)
Urinary frequency/urgency	2/12 (16.7%)
Reproductive system and breast disorders
Breast, pain	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/12 (25%)
Throat/pharynx/larynx, pain	1/12 (8.3%)
Bronchospasm, wheezing	1/12 (8.3%)
Cough	8/12 (66.7%)
Dyspnea	9/12 (75%)
Skin and subcutaneous tissue disorders
Dry skin	1/12 (8.3%)
Hypopigmentation	1/12 (8.3%)
Pruritus/itching	6/12 (50%)
Rash/desquamation	3/12 (25%)

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.