Recurrent Breast CarcinomaPhase 1NCT01606241
Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
A Phase 1 study testing Cyclophosphamide, Laboratory Biomarker Analysis and Multi-epitope Folate Receptor Alpha Peptide Vaccine in people with Recurrent Breast Carcinoma and Recurrent Fallopian Tube Carcinoma, run by Mayo Clinic at 1 site in United States.
Trial summary
This phase I clinical trial studies the side effects of vaccine therapy and cyclophosphamide in treating patients with stage II-III breast cancer or stage II-IV ovarian, primary peritoneal or fallopian tube cancer. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Breast Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma
- What is being tested?
- Cyclophosphamide, Laboratory Biomarker Analysis and Multi-epitope Folate Receptor Alpha Peptide Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jul 2012to 9 Mar 2018
- Phase
- Phase 1
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinically confirmed no evidence of disease >= 90 days from completion of systemic therapy with the exception of hormonal therapy and bisphosphonates (per practice guidelines for breast and ovarian cancer)
- Histological or cytological confirmation of stage II or III breast cancer or stage II, III, or IV ovarian/primary peritoneal/fallopian tube cancer; Note: patients with stage IV ovarian/primary peritoneal/fallopian tube cancer must register within one year of completing chemotherapy
- Completed systemic treatment (chemotherapy, immune modulators [such as trastuzumab], radiation, and/or corticosteroids) with the exception of hormonal therapy and bisphosphonates >= 90 days prior to registration
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelets >= 100,000/ul
Show all 19Show fewer
- Hemoglobin >= 10.0 g/dL
- Creatinine =< 1.5 x upper limit of normal (ULN) or 24 hour urine =< grade 2
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN
- Serum albumin >= 3 g/dL
- Urinalysis with =< 2+ proteinuria
- Thyroid-stimulating hormone (TSH) - negative or =< normal institutional range
- Anti-nuclear antibody (ANA) - negative or =< normal institutional range
- Serum rheumatoid factor (RF) - negative or =< normal institutional range
- Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Capable of understanding the investigative nature, potential risks, and benefits of the study and capable of providing valid informed consent
- Willing to return to Mayo Clinic Rochester for follow-ups (immunizations, blood draws, etc.)
- Willing to provide mandatory blood samples for primary and correlative goals
- Willing to receive a tetanus vaccination if you have not had one within the past year
Who cannot join
- Any of the following:
- Pregnant women
- Nursing women unwilling to stop breast feeding
- Men or women of childbearing potential who are unwilling to employ adequate contraception from the time of registration through cycle 6 (or the final vaccine cycle for each patient)
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
Show all 17Show fewer
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent
- Other active malignancy =< 5 years prior to registration; EXCEPTIONS: Non-melanoma skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for this cancer
- Known history of autoimmune disease
- Any contraindication to receiving sargramostim (GM-CSF) or cyclophosphamide
- Uncontrolled acute or chronic medical conditions including, but not limited to the following:
- Active infection requiring antibiotics
- Congestive heart failure (New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease)
- Myocardial infarction or stroke within previous 6 months
- Use of a systemic steroid =< 30 days prior to registration
- Receiving thyroid replacement therapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of the Safety and Immunogenicity of a Multi-epitope Folate Receptor Alpha Peptide Vaccine Used in Combination With Cyclophosphamide in Subjects Previously Treated for Breast or Ovarian Cancer
This phase I clinical trial studies the side effects of vaccine therapy and cyclophosphamide in treating patients with stage II-III breast cancer or stage II-IV ovarian, primary peritoneal or fallopian tube cancer. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vaccine therapy and cyclophosphamide may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety of administering one cycle of cyclophosphamide and six subsequent monthly vaccinations with a peptide-based vaccine targeting folate receptor (FR)-alpha (multi-epitope folate receptor alpha peptide vaccine).
II. To assess the ability of this vaccination protocol to elicit an immune response as measured by activated FR-alpha-specific T lymphocytes or high-affinity antibodies.
SECONDARY OBJECTIVES:
- To determine FR-alpha expression status of primary tumors when available as formalin-fixed, paraffin-embedded material and whether expression correlates with the ability to generate an immune response.
II. To identify human lymphocyte antigen (HLA) class I binding peptides from FR-alpha that are recognized by lymphocytes from patients prior to and after vaccination.
III. To determine whether cyclophosphamide treatment, prior to vaccination, results in regulatory T cell depletion by assessing regulatory T cells before and immediately after cyclophosphamide treatment.
IV. To compare FR-alpha (FRa) expression levels in tumor removed at primary surgery to FRa expression levels in tumor removed for clinical purposes at disease recurrence. (For ovarian cancer patients whose disease recurs.)
OUTLINE:
Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21 of course 1. Within 3-5 days, patients receive multi-epitope folate receptor alpha peptide vaccine intradermally (ID) on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, and 12 months.
- Conditions
- Recurrent Breast Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Stage IIA Breast Cancer, Stage IIA Fallopian Tube Cancer
- Being tested
- Cyclophosphamide, Laboratory Biomarker Analysis, Multi-epitope Folate Receptor Alpha Peptide Vaccine
- Medical subject headings
- Breast Neoplasms, Fallopian Tube Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Multi-epitope Folate Receptor Alpha Peptide VaccineBiological
Also called FR Alpha Peptide Vaccine
Given ID
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cyclophosphamide and vaccine therapy) | Experimental | Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of course 1. Within 3-5 days, patients receive multi-epitope folate receptor alpha peptide vaccine ID on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Multi-epitope Folate Receptor Alpha Peptide Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who experience severe toxicities (grades 3-5 of the National Cancer Institute's Cancer Therapy Evaluation Program [CTEP] Common Terminology Criteria for Adverse Events, version 4.0)
Defined as adverse events that are classified as either unrelated, unlikely to be related, possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns.
Measured: Up to 12 months
Secondary outcomes (4)
Disease-free survival
The distribution of disease-free survival will be estimated using the method of Kaplan-Meier for each disease group (breast cancer; ovarian cancer).
Measured: Time from registration to documentation of disease recurrence, second primary, or death without disease recurrence or second primary, assessed up to 12 months
FRa expression
A 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FRa positive disease. Similarly, a 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FRa negative disease.
Measured: Up to 12 months
Overall survival time
The distribution of overall survival times will be estimated using the method of Kaplan-Meier for each disease group (breast cancer; ovarian cancer).
Measured: Time from registration to death due to any cause, assessed up to 12 months
Percentage change in plasma concentration of cytokines and chemokines
The percent change in plasma concentrations of cytokines and chemokines from pre-treatment concentrations will be determined. Will be plotted against time with the points belonging to a particular individual connected. Each graph will be visually inspected for trends across time and difference between treatment regimens.
Measured: Baseline to up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2012 (estimated)
- Study start24 Jul 2012
- Primary completion25 Sep 2014
- Study completion9 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Breast CarcinomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthew S. Block, M.D., Ph.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01606241
- Sponsor's protocol ID
- MC1015
- Other IDs
- NCI-2012-00586, MC1015
- Status last verified
- Aug 2024
- First submitted
- 23 May 2012
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of the Safety and Immunogenicity of a Multi-epitope Folate Receptor Alpha Peptide Vaccine Used in Combination With Cyclophosphamide in Subjects Previously Treated for Breast or Ovarian Cancer
- ClinicalTrials.gov ID
- NCT01606241
- Acronym / sponsor ID
- MC1015
- Conditions
- Recurrent Breast Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Stage IIA Breast Cancer, Stage IIA Fallopian Tube Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 24 Jul 2012 (actual)
- Primary completion
- 25 Sep 2014 (actual)
- Study completion
- 9 Mar 2018 (actual)
- First posted
- 25 May 2012 (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 phase I clinical trial studies the side effects of vaccine therapy and cyclophosphamide in treating patients with stage II-III breast cancer or stage II-IV ovarian, primary peritoneal or fallopian tube cancer. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vaccine therapy and cyclophosphamide may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety of administering one cycle of cyclophosphamide and six subsequent monthly vaccinations with a peptide-based vaccine targeting folate receptor (FR)-alpha (multi-epitope folate receptor alpha peptide vaccine).
II. To assess the ability of this vaccination protocol to elicit an immune response as measured by activated FR-alpha-specific T lymphocytes or high-affinity antibodies.
SECONDARY OBJECTIVES:
- To determine FR-alpha expression status of primary tumors when available as formalin-fixed, paraffin-embedded material and whether expression correlates with the ability to generate an immune response.
II. To identify human lymphocyte antigen (HLA) class I binding peptides from FR-alpha that are recognized by lymphocytes from patients prior to and after vaccination.
III. To determine whether cyclophosphamide treatment, prior to vaccination, results in regulatory T cell depletion by assessing regulatory T cells before and immediately after cyclophosphamide treatment.
IV. To compare FR-alpha (FRa) expression levels in tumor removed at primary surgery to FRa expression levels in tumor removed for clinical purposes at disease recurrence. (For ovarian cancer patients whose disease recurs.)
OUTLINE:
Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21 of course 1. Within 3-5 days, patients receive multi-epitope folate receptor alpha peptide vaccine intradermally (ID) on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, and 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cyclophosphamide and vaccine therapy) | Experimental | Drug: Cyclophosphamide, Other: Laboratory Biomarker Analysis, Biological: Multi-epitope Folate Receptor Alpha Peptide VaccinePatients receive cyclophosphamide PO BID on days 1-7 and 15-21 of course 1. Within 3-5 days, patients receive multi-epitope folate receptor alpha peptide vaccine ID on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Clinically confirmed no evidence of disease >= 90 days from completion of systemic therapy with the exception of hormonal therapy and bisphosphonates (per practice guidelines for breast and ovarian cancer)
- Histological or cytological confirmation of stage II or III breast cancer or stage II, III, or IV ovarian/primary peritoneal/fallopian tube cancer; Note: patients with stage IV ovarian/primary peritoneal/fallopian tube cancer must register within one year of completing chemotherapy
- Completed systemic treatment (chemotherapy, immune modulators [such as trastuzumab], radiation, and/or corticosteroids) with the exception of hormonal therapy and bisphosphonates >= 90 days prior to registration
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Absolute neutrophil count (ANC) >= 1500/mm^3
Key exclusion criteria (17 listed)
- Any of the following:
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent
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 |
|---|---|---|
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven PO | Drug | Treatment (cyclophosphamide and vaccine therapy) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (cyclophosphamide and vaccine therapy) |
| Multi-epitope Folate Receptor Alpha Peptide VaccineAlso: FR Alpha Peptide VaccineGiven ID | Biological | Treatment (cyclophosphamide and vaccine therapy) |
Primary outcome
Proportion of patients who experience severe toxicities (grades 3-5 of the National Cancer Institute's Cancer Therapy Evaluation Program [CTEP] Common Terminology Criteria for Adverse Events, version 4.0)
Time frame: Up to 12 months
Defined as adverse events that are classified as either unrelated, unlikely to be related, possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns.
4 secondary outcomes
Disease-free survival
Time frame: Time from registration to documentation of disease recurrence, second primary, or death without disease recurrence or second primary, assessed up to 12 months
FRa expression
Time frame: Up to 12 months
Overall survival time
Time frame: Time from registration to death due to any cause, assessed up to 12 months
Percentage change in plasma concentration of cytokines and chemokines
Time frame: Baseline to up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
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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.
Matthew S. Block, M.D., Ph.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cyclophosphamide, Laboratory Biomarker Analysis and Multi-epitope Folate Receptor Alpha Peptide Vaccine in people with Recurrent Breast Carcinoma and Recurrent Fallopian Tube Carcinoma, run by Mayo Clinic 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 19 inclusion and 17 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: finished, as of the sponsor's last update on 21 Aug 2024. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of patients who experience severe toxicities (grades 3-5 of the National Cancer Institute's Cancer Therapy Evaluation Program [CTEP] Common Terminology Criteria for Adverse Events, version 4.0) (time frame: Up to 12 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 21 Aug 2024.