Breast CancerPhase 1/2NCT00090480
Vaccine Treatment for Advanced Breast Cancer
A Phase 1/2 study testing HyperAcute - Breast cancer vaccine in people with Breast Cancer, run by NewLink Genetics Corporation at 1 site in United States.
Trial summary
This 2-phase study will determine the safety of treating patients with breast cancer with the genetically engineered HyperAcute-Breast cancer vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- HyperAcute - Breast cancer vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Sep 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological diagnosis of infiltrating breast carcinoma, including infiltrating ductal carcinoma, lobular carcinoma, medullary carcinoma, colloid, comedocarcinoma, papillary, inflammatory carcinoma, signet ring carcinoma. The patient's pathology must be reviewed and confirmed by Iowa Methodist Medical Center's or Mercy Medical Center's Pathology Department.
- AJCC Stage IV (any T, any N, M1), metastatic, progressive or recurrent breast carcinoma. Patients may not be eligible for other curative intent treatment (e.g. surgical resection). Patients must have failed one salvage treatment.
- Eastern Cooperate Oncology Group Performance Status less than or equal to 2.
- Serum albumin greater than or equal to 3.0 gm/dL.
- Expected survival greater than or equal to 6 months.
- Subjects must have a negative serology for Hep B, C and HIV prior to entering study.
Show all 16Show fewer
- Adequate organ function including: Marrow: Hemoglobin greater than or equal to 10.0 mg/dL, absolute granulocyte count (AGC) greater than or equal to 1,500/mm(3), platelets greater than or equal to 100,000/mm(3), absolute lymphocyte count greater than or equal to 475/mm(3). Hepatic: serum total bilirubin less than or equal to 1.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) less than or equal to 2.5 x ULN. Renal: serum creatinine less than or equal to 1.5 x ULN or creatinine clearance greater than or equal to 50 mL/min.
- All on-study tests must be less than or equal to Grade I toxicity for patient to be eligible for study, excluding serum LDH levels. PT, PTT must be less than or equal to 1.5 x ULN except for patients who are on therapeutic anticoagulant therapy.
- Measurable or non-measurable disease as defined as:
- Measurable - those that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques (CT, MRI, x-ray) or as greater than or equal to 10 mm with spiral CT scan. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters).
- Non-measurable - All other lesions (or sites of disease), including small lesions (longest diameter less than 20 mm with conventional techniques or less than 10 mm using spiral CT scan), are considered non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural or pericardial effusions, lymphangitis cutis or pulmonis, inflammatory breast disease, abdominal masses (not followed by CT or MRI), and cystic lesions are all considered non-measurable.
- Prior therapy for breast cancer that may include surgery, radiation therapy, and/or less than or equal to 2 different cytotoxic chemotherapy regimens (including neoadjuvant and adjuvant treatment). Patients receiving preoperative (neoadjuvant) and postoperative (within 12 weeks of surgery) adjuvant chemotherapy with the same agent(s) will be considered to have received a single chemotherapy regimen.
- Patients with previously treated, unresponsive or progressive disease that have failed at least one salvage regimen.
- Patients must be greater than or equal to 4 weeks since major surgery, radiotherapy, chemotherapy (6-weeks if they were treated with a nitrosourea or mitomycin) and recovered from the toxicity of prior treatment to less than or equal to Grade 1, exclusive of alopecia or fatigue.
- Patients must have the ability to understand the study, its risks, side effects, potential benefits and is able to give written informed consent to participate. Patients may not be consented by a durable power of attorney (DPA).
- Male and female subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental drug, and for one month after the last immunization.
Who cannot join
- Age less than 18-years-old.
- Active CNS metastases or carcinomatous meningitis.
- Hypercalcemia greater than 2.9 mmol/L, unresponsive to standard therapy (e.g., I.V. hydration, diuretics, calctonin and/or bisphosphate therapy).
- Pregnant or nursing women due to the unknown effects of vaccination on the developing fetus or newborn infant.
- Other malignancy within five years, unless the probability of recurrence of the prior malignancy is less than 5%. Patient's curatively treated for squamous and basal cell carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or patients with a history of malignant tumor in the past that have been disease free for at least five years are also eligible for this study.
- History of organ transplant or current active immunosuppressive therapy (such as cyclosporine, tacrolimus, etc.) or history of prior immunotherapy except Herceptin and/or other monoclonal antibody therapies.
Show all 14Show fewer
- Subjects taking systemic corticosteroid therapy for any reason including replacement therapy for hypoadrenalism, are not eligible. Subjects receiving inhaled or topical corticosteroids are eligible. Subjects who require systemic corticosteroids after beginning vaccinations, will be removed from the study.
- Significant or uncontrolled congestive heart failure (CHF), myocardial infarction, significant ventricular arrhythmias within the last six months or significant pulmonary dysfunction.
- Active infection or antibiotics within 1-week prior to study, including unexplained fever (temp. greater than 38.1 degrees Celsius).
- Autoimmune disease (e.g., systemic lupus erythematosis, active rheumatoid arthritis, etc). Patients with a remote history of asthma or mild active asthma are eligible.
- Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis).
- Any condition, psychiatric or otherwise, that would preclude informed consent consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc).
- A known allergy to any component of the alpha (1,3) galactosyltransferase tumor vaccine or cell lines from which it is derived.
- Patients having undergone splenectomy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical Oncology Hematology Associates
Des Moines, Iowa, 50309
About this study
Official title: A Phase I/II Study of an Antitumor Vaccination Using Alpha(1,3)Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Relapsed or Refractory Breast Cancer
This 2-phase study will determine the safety of treating patients with breast cancer with the genetically engineered HyperAcute-Breast cancer vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed breast cancer cells containing a mouse gene that causes the production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the immune response to the foreign substance will stimulate the immune system to attack the patient's own cancer cells that have similar proteins without this sugar pattern, causing the tumor to remain stable or shrink.
Patients 18 years of age or older with breast cancer that has recurred or no longer responds to standard treatment may be eligible for this study. Candidates will be screened with medical history and physical examination, blood tests, urinalysis, chest x-rays and CT scans. MRI, PET, and ultrasound scans may be obtained if needed.
Read more
Participants will receive four vaccinations a month apart from each other. The vaccines will be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of the study will treat successive groups of patients with increasing numbers of the vaccine cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will look for any beneficial effects of the vaccine given at the highest dose found to be safe in Phase I. Weekly blood samples will be drawn during the 4 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 2 months for the first year after vaccination and then every 3 months for the next 2 years for the following tests and procedures to evaluate treatment response and side effects:
- Medical history and physical examination
- Blood tests
- X-rays and various scans (nuclear medicine/CT/MRI)
- FACT-B Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, before each vaccination, and during follow-up visits after completing the treatment. It includes questions on the severity of breast cancer symptoms and the ability to perform normal activities of daily life.
Read the detailed description
According to 2002 statistics of the American Cancer Society, an estimated 203,500 individuals will be diagnosed with breast cancer and 39,600 will die of the disease this year despite all current therapy. This protocol attempts to exploit an approach to breast cancer gene therapy using a naturally occurring barrier to xenotransplantation in humans in attempt to vaccinate patients against their breast cancer. The expression of the murine alpha (1,3) galactosyltransferase [alpha (1,3) GT] gene results in the cell surface expression of alpha (1,3) galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation. These antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with relapsed or refractory breast cancer will undergo a series of four intradermal injections with a vaccine composed of irradiated allogeneic breast cancer cell lines (HAB-1 and HAB-2) that have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine alpha (1,3) GT gene. Endpoints of the study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and immunological responses.
- Conditions
- Breast Cancer
- Being tested
- HyperAcute - Breast cancer vaccine
- Keywords
- Cancer
- Medical subject headings
- Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HyperAcute - Breast cancer vaccineBiological
Also called HAB-1 and HAB-2 vaccine components
Cells will be injected intradermally for four weeks for four cycles. Dosage will vary from 10 million to 100 million HAB cells.
| Study group | Role | What they receive |
|---|---|---|
| Vaccine group | Experimental | Not described Receives: Biological: HyperAcute - Breast cancer vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and efficacy of administration of HyperAcute Breast (HAB) cancer cells by injection into women with recurrent or refractory breast carcinoma
Measured: 4 months
Secondary outcomes (1)
To conduct correlative scientific studies of patient samples to determine the mechanism of any observed anti-tumor effect.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2004 (estimated)
- Study startAug 2004
- Primary completionSep 2007
- Study completionSep 2007
Why it stopped: Enrollment goals unable to be reached.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewLink Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Charles J. Link, Jr., M.D., Study chair, NewLink Genetics Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00090480
- Sponsor's protocol ID
- NLG0102
- Other IDs
- 20031968
- Status last verified
- May 2020
- First submitted
- 26 Aug 2004
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of an Antitumor Vaccination Using Alpha(1,3)Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Relapsed or Refractory Breast Cancer
- ClinicalTrials.gov ID
- NCT00090480
- Acronym / sponsor ID
- NLG0102
- Conditions
- Breast Cancer
- Keywords
- Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment goals unable to be reached.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- NewLink Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- Aug 2004
- Primary completion
- Sep 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 31 Aug 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 2-phase study will determine the safety of treating patients with breast cancer with the genetically engineered HyperAcute-Breast cancer vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed breast cancer cells containing a mouse gene that causes the production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the immune response to the foreign substance will stimulate the immune system to attack the patient's own cancer cells that have similar proteins without this sugar pattern, causing the tumor to remain stable or shrink.
Patients 18 years of age or older with breast cancer that has recurred or no longer responds to standard treatment may be eligible for this study. Candidates will be screened with medical history and physical examination, blood tests, urinalysis, chest x-rays and CT scans. MRI, PET, and ultrasound scans may be obtained if needed.
Participants will receive four vaccinations a month apart from each other. The vaccines will be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of the study will treat successive groups of patients with increasing numbers of the vaccine cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will look for any beneficial effects of the vaccine given at the highest dose found to be safe in Phase I. Weekly blood samples will be drawn during the 4 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 2 months for the first year after vaccination and then every 3 months for the next 2 years for the following tests and procedures to evaluate treatment response and side effects:
- Medical history and physical examination
- Blood tests
- X-rays and various scans (nuclear medicine/CT/MRI)
- FACT-B Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, before each vaccination, and during follow-up visits after completing the treatment. It includes questions on the severity of breast cancer symptoms and the ability to perform normal activities of daily life.
Detailed description
According to 2002 statistics of the American Cancer Society, an estimated 203,500 individuals will be diagnosed with breast cancer and 39,600 will die of the disease this year despite all current therapy. This protocol attempts to exploit an approach to breast cancer gene therapy using a naturally occurring barrier to xenotransplantation in humans in attempt to vaccinate patients against their breast cancer. The expression of the murine alpha (1,3) galactosyltransferase [alpha (1,3) GT] gene results in the cell surface expression of alpha (1,3) galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation. These antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with relapsed or refractory breast cancer will undergo a series of four intradermal injections with a vaccine composed of irradiated allogeneic breast cancer cell lines (HAB-1 and HAB-2) that have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine alpha (1,3) GT gene. Endpoints of the study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and immunological responses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vaccine group | Experimental | Biological: HyperAcute - Breast cancer vaccine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histological diagnosis of infiltrating breast carcinoma, including infiltrating ductal carcinoma, lobular carcinoma, medullary carcinoma, colloid, comedocarcinoma, papillary, inflammatory carcinoma, signet ring carcinoma. The patient's pathology must be reviewed and confirmed by Iowa Methodist Medical Center's or Mercy Medical Center's Pathology Department.
- AJCC Stage IV (any T, any N, M1), metastatic, progressive or recurrent breast carcinoma. Patients may not be eligible for other curative intent treatment (e.g. surgical resection). Patients must have failed one salvage treatment.
- Eastern Cooperate Oncology Group Performance Status less than or equal to 2.
- Serum albumin greater than or equal to 3.0 gm/dL.
- Expected survival greater than or equal to 6 months.
Key exclusion criteria (14 listed)
- Age less than 18-years-old.
- Active CNS metastases or carcinomatous meningitis.
- Hypercalcemia greater than 2.9 mmol/L, unresponsive to standard therapy (e.g., I.V. hydration, diuretics, calctonin and/or bisphosphate therapy).
- Pregnant or nursing women due to the unknown effects of vaccination on the developing fetus or newborn infant.
- Other malignancy within five years, unless the probability of recurrence of the prior malignancy is less than 5%. Patient's curatively treated for squamous and basal cell carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or patients with a history of malignant tumor in the past that have been disease free for at least five years are also eligible for this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HyperAcute - Breast cancer vaccineAlso: HAB-1 and HAB-2 vaccine componentsCells will be injected intradermally for four weeks for four cycles. Dosage will vary from 10 million to 100 million HAB cells. | Biological | Vaccine group |
Primary outcome
To determine the safety and efficacy of administration of HyperAcute Breast (HAB) cancer cells by injection into women with recurrent or refractory breast carcinoma
Time frame: 4 months
1 secondary outcome
To conduct correlative scientific studies of patient samples to determine the mechanism of any observed anti-tumor effect.
Time frame: 4 months
Results and safety
The study was stopped early (reason given: Enrollment goals unable to be reached.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles J. Link, Jr., M.D. study chair
NewLink Genetics Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HyperAcute - Breast cancer vaccine in people with Breast Cancer, run by NewLink Genetics Corporation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Enrollment goals unable to be reached.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the safety and efficacy of administration of HyperAcute Breast (HAB) cancer cells by injection into women with recurrent or refractory breast carcinoma (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020.