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SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03066947
Recruitment Status : Recruiting
First Posted : March 1, 2017
Last Update Posted : February 6, 2018
Cancer Insight, LLC
Information provided by (Responsible Party):
BriaCell Therapeutics Corporation

Brief Summary:
This is a single arm, open label study of SV-BR-1-GM, a targeted immunotherapy for breast cancer. Eligible patients will have histological confirmation of breast cancer with recurrent and/or metastatic lesions. The treatment regimen includes a pre-treatment with low-dose cyclophosphamide 2-3 days before the inoculation; inoculation in 4 sites on the thighs and upper back; and post-treatment inoculation of Interferon-alpha-2b into the sites of inoculation ~2 and ~4 days after the inoculation. These is repeated every 2 weeks for one month (3 treatments), then monthly for up to one year. Standard tumor assessments are performed at baseline and then every 2-3 months.

Condition or disease Intervention/treatment Phase
Breastcancer Breast Neoplasm Biological: SV-BR-1-GM Drug: Cyclophosphamide Biological: Interferon-alpha-2b Phase 1 Phase 2

Detailed Description:

This is a single arm, open label study of SV-BR-1-GM in recurrent and/or metastatic breast cancer. The detailed treatment regimen follows:

Pre-Inoculation Regimen:

Cyclophosphamide (Cytoxan) 300 mg/m^2 I.V., 1x only, will be given 48-72 hours before each SV-BR-1-GM inoculation, with an antiemetic of the provider's choice (steroids prohibited). If the patient is not tolerating the cyclophosphamide, a lower dose may be used (e.g. 200 or 150 mg/m^2) or it may be withheld, with the Sponsor's approval.

Innoculation Day Standard Operating Procedures:

  1. Inquire regarding events of past weeks, change in medications, pain scale, ECOG scale, and review of systems.
  2. Check injection sites.
  3. Perform DTH skin test intra-dermally with the SV-BR-1 parent cell line (~1 x 10^6 irradiated tumor cells). Observe about 20 minutes for acute hypersensitivity. Grade III or higher acute hypersensitivity will abort therapy.
  4. Inject SV-BR-1-GM intra-dermally into 4 sites in thighs and upper back (0.5 mL each). Monitor patients for 60 minutes. Vital signs will be assessed and medical attention will be warranted if unstable.

SV-BR-1-GM Preparation & Inoculation Regimen:

Each inoculation will be administered via intra-dermal injection at the investigational sites. Subjects will receive 15-25 x 10^6 viable, irradiated transfected breast tumor cells in a total volume of 2.0 ml Ringer's lactate. SV-BR-1-GM cells will be irradiated to ensure cell replication incompetency.

SV-BR-1-GM will be divided into four aliquots of 0.5 mL each and injected intra-dermally; one each into the anterior skin of the subject's right and left thighs and over the right and left upper back . Application of anesthetic lidocaine crème may be used if necessary for control of local pain before inoculation. Subjects will be monitored for 60 minutes.

After at least 10 subjects have been treated safely with this regimen, the dose of SV-BR-1-GM may be escalated or decreased in subsequent patients based on the emerging data.

Post-Inoculation Regimen:

2 days (± 1 day) after inoculation, and again 4 days (± 1 day) later after inoculation, the patient will return to the principal investigator's office to receive Interferon-alpha-2b (Merck) in 0.1 mL saline, prepared as follows: These will also be provided by the sponsor and injected intra-dermally to each inoculation site, beneath the thickest area. Again, subjects will be observed about 20 minutes. The DTH response will also be recorded at the 2 days (± 1 day) visit.

This cycle will be performed every 2 weeks for the first month of treatment (3 inoculations), and then every month for up to one year.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa Study of SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer Patients
Actual Study Start Date : May 5, 2017
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: SV-BR-1-GM Monotherapy
Pretreatment with low dose cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation; SV-BR-1-GM inoculation intradermally in 4 sites on the upper back (x2) and thighs (x2); Post-inoculation low dose Interferon-alpha-2b into the vaccination sites ~2 and ~4 days after SV-BR-1-GM inoculation
Biological: SV-BR-1-GM
See above
Drug: Cyclophosphamide
Low dose pre-treatment to reduce regulatory T cells
Other Name: Cytoxan
Biological: Interferon-alpha-2b
Low dose given in the vaccine site to boost the immune response
Other Name: Intron A

Primary Outcome Measures :
  1. Incidence of Treatment Emergent Adverse Events [Safety] [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the incidence of toxicity events while on SV-BR-1-GM, as defined by CTCAE

Secondary Outcome Measures :
  1. Duration of Treatment Emergent Adverse Events [Safety] [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the duration of toxicity events while on SV-BR-1-GM, as defined by CTCAE

  2. Relationship of Adverse Events to SV-BR-1-GM [Safety] [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the relationship of toxicity events, as defined by CTCAE, to SV-BR-1-GM administration

  3. Objective Tumor Response Rate [ Time Frame: Through study completion, an average of 1 year ]
    Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) and immune-related RECIST (iRECIST) criteria.

  4. Rate of Non-progression of Tumors [ Time Frame: Through study completion, an average of 1 year ]
    Non-progressive rate, defined as CR, PR or stable disease (SD) per RECIST and iRECIST criteria

  5. Durability of Tumor Response [ Time Frame: Through study completion, an average of 1 year ]
    Durability of response, by evaluating those patients eligible to complete the optional treatments from 9-12 months

Other Outcome Measures:
  1. Immune responses to vaccine [ Time Frame: Through study completion, an average of 1 year ]
    To assess immune responses to SV-BR-1-GM, and to recall antigens, if any, as measured by DTH skin tests and/or other immunological tests

  2. Quality of Life using the SF-36 Health Survey [ Time Frame: Through study completion, an average of 1 year ]
    To measure the quality of life (QOL) of participants using the SF-36 Health Survey, which includes measures of General Health, Limitations of Activity, Physical Health Problems, Emotional Health Problems, Social Activities, Energy and Emotions.

  3. Weight [ Time Frame: Through study completion, an average of 1 year ]
    To measure changes in weight.

  4. Performance status [ Time Frame: Through study completion, an average of 1 year ]
    To measure changes in performance status using the Eastern Cooperative Oncology Group (ECOG) scale

  5. Pain (pain scale) [ Time Frame: Through study completion, an average of 1 year ]
    To measure changes in pain using a scale from None to Very Mild to Mild to Moderate to Severe to Very Severe

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • 1. Have histological confirmation of breast cancer with recurrent and/or metastatic lesions via investigational site.

    • Patients with new or progressive breast cancer metastatic to brain will be eligible provided:

      1. There is no need for steroids and patients have not had steroids at least 2 weeks
      2. No individual tumor size is >50 mm3
      3. ECOG status <3
      4. Tumor is not impinging on Middle Cerebral Artery/speech-motor strip
      5. If surgically debulked, must be healed from surgery and at least 3 weeks have elapsed since general anesthesia
      6. Patients consent to MRI studies at 3-4 week intervals until evidence of tumor regression on at least 2 imaging studies. In no case, will the interval between MRI studies be longer than 3 months. MRI study may be introduced at any time should the patients develop new or clearly worsening symptoms and/or introduction of steroids

        2. Have evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after failing at least one course of community standard systemic treatment with chemotherapy (and endocrine therapy if appropriate)

        3. Be 18 years of age or older and female

        4. Have expected survival of at least 4 months

        5. Have adequate performance status (ECOG 0-2)

        6. Patients may be maintained on hormonal therapy provided there is clear evidence of tumor progression

        7. Have provided written informed consent.

        Exclusion Criteria:

    1. Concurrent or recent chemotherapy (within 3 weeks), XRT within 3 weeks, may have had immunotherapy in the past (off within 3 weeks), or general anesthesia/major surgery (within 3 weeks). Patients must have recovered from all known or expected toxicities from previous treatment and passed a treatment-free "washout" period of 3 weeks before starting this program (8 weeks for persons receiving nitrosourea or mitomycin).
    2. History of clinical hypersensitivity to GM-CSF, Interferon-alpha-2b (Merck), yeast, beef, or to any components used in the preparation of the experimental vaccine.
    3. BUN >30 and a creatinine >2.
    4. Absolute granulocyte count < 1000; platelets <100,000.
    5. Bilirubin >2.0; alkaline phosphatase >5x upper limit of normal (ULN); ALT/AST >2x ULN.
    6. Proteinuria >1+ on urinalysis or >1 gm/24hr.
    7. Left ventricular ejection fraction (LVEF as determined by cardiac echo or MUGA scan) below the normal limits of the institutions specific testing range. This assessment may be repeated once at the discretion of the Investigator with the approval of the Sponsor.
    8. New York Heart Association stage 3 or 4 cardiac disease.
    9. A pleural effusion of moderate severity or worse.
    10. Any woman of childbearing potential, unless she:

      1. Agrees to take measures to avoid becoming pregnant during the study and
      2. Has a negative serum pregnancy test within 7 days prior to starting treatment.
    11. Women who are pregnant or nursing.
    12. Patients with concurrent second malignancy. Persons with previous malignancies effectively treated and not requiring treatment for >24 months are eligible, provided there is unambiguous documentation that current local recurrence or metastatic site represents recurrence of the primary breast malignancy.
    13. Patients who are HIV positive (by self-report) or have clinical or laboratory features indicative of AIDS.
    14. Patients who require anticoagulation, systemic steroids, statin therapy or beta-blocker therapy. The beta-blocker might compromise use of epinephrine for the rare possibility of anaphylaxis. Hypertension controlled by other agents does not disqualify, provided other criteria are met.
    15. Patients who are on treatment for rheumatological or autoimmune disease unless approved by the Investigator in consultation with the Sponsor (e.g., as for replacement therapy for autoimmune thyroiditis or diabetes).
    16. Patients with severe psychiatric (i.e. schizophrenia, bipolar, or borderline personality disorder) or other clinically progressive major medical problems, unless approved by the PI.
    17. Male breast cancer patients.
    18. Patients may not be on a concurrent clinical trial, unless approved by PI.

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 identifier (NCT number): NCT03066947

Contact: Karen Arrington, RN BSN CCRP 210-243-5711
Contact: George E Peoples, MD, FACS 210.557.4291

United States, California
St. Joseph Heritage Healthcare Recruiting
Santa Rosa, California, United States, 95403
Contact: Jennafer Carlin-Rosset, MPH    707-521-3830   
Contact: Kim Young, RN, CCRC    707-521-3830   
Principal Investigator: Jarrod P Holmes, M.D.         
United States, Florida
Florida Cancer Care Recruiting
Plantation, Florida, United States, 33324
Contact: Filiz Gokce, F.M.D.    954-582-1850   
Principal Investigator: Elizabeth Tan-Chiu, M.D., P.A.         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Rita Murphy, MA, MPH    215-955-9626   
Principal Investigator: Saveri Bhattacharya, DO         
United States, Washington
Providence Regional Medical Center Recruiting
Everett, Washington, United States, 98201
Contact: Rachel Macomber, CMA    425-297-5532   
Contact: Katie Lyon    Lyon   
Principal Investigator: Jason Lukas, MD, PhD         
Sponsors and Collaborators
BriaCell Therapeutics Corporation
Cancer Insight, LLC
Study Director: George E Peoples, MD, FACS Cancer Insight, LLC

Additional Information:
Responsible Party: BriaCell Therapeutics Corporation Identifier: NCT03066947     History of Changes
Other Study ID Numbers: 0001
WRI-GEV-007 ( Other Identifier: BriaCell )
First Posted: March 1, 2017    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antiviral Agents
Anti-Infective Agents