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Trial record 47 of 207 for:    Oral Cancer | Recruiting Studies | NIH

Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT03012100
Recruitment Status : Recruiting
First Posted : January 6, 2017
Last Update Posted : August 16, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Academic and Community Cancer Research United

Brief Summary:
This randomized phase II trial studies how well multi-epitope folate receptor alpha peptide vaccine, sargramostim, and cyclophosphamide work in treating patients with triple negative breast cancer. Vaccines made from a person's white blood cells mixed with tumor proteins 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 multi-epitope folate receptor alpha peptide vaccine, sargramostim, and cyclophosphamide may work better in treating patients with triple negative breast cancer.

Condition or disease Intervention/treatment Phase
Bilateral Breast Carcinoma Estrogen Receptor Negative HER2/Neu Negative Progesterone Receptor Negative Stage IB Breast Cancer AJCC v7 Stage II Breast Cancer AJCC v6 and v7 Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage III Breast Cancer AJCC v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage IV Breast Cancer AJCC v6 and v7 Triple-Negative Breast Carcinoma Unilateral Breast Carcinoma Drug: Cyclophosphamide Other: Laboratory Biomarker Analysis Biological: Multi-epitope Folate Receptor Alpha Peptide Vaccine Other: Placebo Biological: Sargramostim Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To show that multi-epitope folate receptor alpha peptide vaccine (folate receptor [FR]alpha peptide vaccine) with sargramostim (GM-CSF) adjuvant will prolong the disease-free survival (DFS) compared to GM-CSF adjuvant treatment in patients with triple negative breast cancer.

SECONDARY OBJECTIVES:

I. To compare the safety and tolerability of metronomic cyclophosphamide followed by FRalpha peptide vaccine with GM-CSF versus GM-CSF alone.

TERTIARY OBJECTIVES:

I. To determine whether high level of antibody and cellular immune response toward the FRalpha measured at baseline is a prognostic factor for vaccine immune response and/or cancer relapse.

II. To determine whether the level of tumor expression of FRalpha at baseline is a prognosis factor for vaccine immune response and/or cancer relapse.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21 of course 1 only. Starting course 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim intradermally (ID) on day 1. Treatment repeats every 28 days for courses 2-7 and every 6 months for courses 8-14 in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cyclophosphamide as in Arm I. Starting course 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for courses 2-7 and every 6 months for courses 8-14 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Double Blind, Parallel Groups, Controlled, Randomized Phase II Trial to Evaluate Vaccination With Folate Receptor Alpha Peptide Vaccine With GM-CSF as Vaccine Adjuvant Following Oral Cyclophosphamide Versus GM-CSF/Placebo to Prevent Recurrence in Patients With Triple Negative Breast Cancer
Actual Study Start Date : March 31, 2017
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm I (FRalpha peptide vaccine, sargramostim)
Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of course 1 only. Starting course 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for courses 2-7 and every 6 months for courses 8-14 in the absence of disease progression or unacceptable toxicity.
Drug: Cyclophosphamide
Given PO
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Multi-epitope Folate Receptor Alpha Peptide Vaccine
Given ID
Other Name: FR Alpha Peptide Vaccine

Biological: Sargramostim
Given ID
Other Names:
  • 23-L-Leucinecolony-Stimulating Factor 2
  • DRG-0012
  • Leukine
  • Prokine
  • rhu GM-CFS
  • Sagramostim
  • Sargramostatin

Placebo Comparator: Arm II (placebo, sagramostim)
Patients receive cyclophosphamide as in Arm I. Starting course 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for courses 2-7 and every 6 months for courses 8-14 in the absence of disease progression or unacceptable toxicity.
Drug: Cyclophosphamide
Given PO
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given ID
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Biological: Sargramostim
Given ID
Other Names:
  • 23-L-Leucinecolony-Stimulating Factor 2
  • DRG-0012
  • Leukine
  • Prokine
  • rhu GM-CFS
  • Sagramostim
  • Sargramostatin




Primary Outcome Measures :
  1. Disease-free survival [ Time Frame: Through study completion (average of 5 years) ]
    Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.


Secondary Outcome Measures :
  1. FRalpha levels [ Time Frame: Through study completion (average of 5 years) ]
    FR alpha levels at baseline will be examined as a prognostic factor in the vaccine immune response. A multivariable Cox proportional hazard model will be used to assess baseline FR alpha levels as a potential prognostic factor for immune response.

  2. Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events 4.0 [ Time Frame: Through study completion (average of 5 years) ]
    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. Will use the Cochran-Mantel Haenszel chi-squared test with study stratification factors. Will use logistic regression to test differences in proportions while controlling for the known covariates.

  3. Overall survival [ Time Frame: Through study completion (average of 5 years) ]
    Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.

  4. Vaccine induced FRalpha-specific T cell responses defined as the proportion of patients with at least a 2-fold increase in the number of cells/plasma concentration [ Time Frame: Through study completion (average of 5 years) ]
    Will be determined along with its corresponding 95% confidence interval.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Completely resected unilateral or bilateral primary carcinoma of the breast without clinical evidence of disease, negative for estrogen receptor (ER) and progesterone receptor (PR) (cut-off for positivity is > 1% positive tumor cells with nuclear staining), and negative for HER2 as defined by one of the four situations delineated below:

    • HER2 immunohistochemistry (IHC) expression of 0 or 1+ and in-situ hybridization non-amplified
    • HER2 IHC expression of 0 or 1+ and in-situ hybridization not done
    • HER2 IHC expression of 2+ and in-situ hybridization non-amplified
    • IHC not done and in-situ hybridization non-amplified
    • Note: central review is not required
  • Completed planned breast surgeries and any radiation therapy >= 30 days prior to randomization
  • Completed last cycle of chemotherapy (which can be given in the adjuvant and/or neoadjuvant setting) >= 60 days but not >= 365 days prior to randomization
  • Patient has at least one of the following:

    • Pathologic N1-3
    • Pathologic T3
    • Neoadjuvant chemotherapy and did not achieve pathologic response at time of surgery
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 75,000/uL
  • Aspartate transaminase (AST) =< 3 x upper limit of normal (ULN)
  • Creatinine =< 1.5 x ULN
  • Urine dipstick proteinuria < 2+ or urine protein/creatinine (UPC) ratio =< 1.0; Note: patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate =< 1 g of protein in 24 hours
  • Negative serum pregnancy test done =< 14 days prior to randomization, for women of childbearing potential only
  • Provide informed written consent
  • Willing to return to enrolling institution for follow-up
  • Willing to provide tissue and blood samples for correlative research studies

Exclusion Criteria:

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception
  • Clinical evidence of local recurrence or distant metastases; Note: all patients must have either a positron emission tomography (PET)/computed tomography (CT) or a CT of chest, abdomen and pelvis and a bone scan; if one or more of these is concerning for distant metastases, follow-up imaging and/or biopsy should be performed to rule out distant metastases prior to randomization
  • Inflammatory breast cancer or tumor with deep adherence or cutaneous invasion
  • Known hypersensitivity reaction to GM-CSF
  • History of auto-immune disease per physician discretion
  • 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
  • Prior secondary malignancy < 5 years prior to consent (except non-melanoma skin cancer or carcinoma in situ of the uterine cervix) or receiving other specific treatment for this cancer (monoclonal antibody, small molecule pathway inhibitor)
  • Treatment with systemic corticosteroid or immune-modulators =< 30 days prior to randomization
  • Concurrent treatment with other experimental drugs or any other systemic anticancer therapy (due to unknown drug-vaccine potential interactions)
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
  • Prior or concurrent use of trastuzumab

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03012100


Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Donald W. Northfelt         
United States, District of Columbia
MedStar Georgetown University Hospital Withdrawn
Washington, District of Columbia, United States, 20007
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Alvaro Moreno-Aspitia         
University of Miami Miller School of Medicine-Sylvester Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Onaidy T Torress    305-243-3379    OTorres@med.miami.edu   
Principal Investigator: Carmen J. Calfa         
United States, Illinois
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Simona Olberkyte    773-702-4848    solberkyte@medicine.bsd.uchicago.edu   
Principal Investigator: Rita Nanda         
Carle Cancer Center NCI Community Oncology Research Program Recruiting
Urbana, Illinois, United States, 61801
Contact: Christine M. Canfield    217-326-1881    christine.canfield@carle.com   
Principal Investigator: Kendrith M. Rowland         
United States, Louisiana
Ochsner Medical Center Jefferson Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Socea A. May    504-842-2373    Socea.may@ochsner.org   
Principal Investigator: John T. Cole         
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Steven Isakoff    617-726-6500    sisakoff@mgh.harvard.edu   
Principal Investigator: Steven J. Isakoff         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referrals Office    855-776-0015      
Principal Investigator: Kathryn J. Ruddy         
United States, Virginia
Inova Fairfax Hospital Recruiting
Falls Church, Virginia, United States, 22042
Contact: Parisa Saifollahi    703-720-5210    Parisa.Saifollahi@inova.org   
Principal Investigator: Mary J. Wilkinson         
United States, Wisconsin
Marshfield Clinic Recruiting
Marshfield, Wisconsin, United States, 54449
Contact: Brenda Maronde    715-389-7542    maronde.brenda@marshfieldresearch.org   
Principal Investigator: Arlene A. Gayle         
Sponsors and Collaborators
Academic and Community Cancer Research United
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kathryn Ruddy Academic and Community Cancer Research United

Responsible Party: Academic and Community Cancer Research United
ClinicalTrials.gov Identifier: NCT03012100     History of Changes
Other Study ID Numbers: RU011501I
NCI-2016-01878 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RU011501I ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: January 6, 2017    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Unilateral Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carcinoma
Breast Diseases
Skin Diseases
Vaccines
Cyclophosphamide
Folic Acid
Vitamin B Complex
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Hematinics
Vitamins
Micronutrients
Growth Substances