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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03066947
Recruitment Status : Completed
First Posted : March 1, 2017
Results First Posted : January 29, 2021
Last Update Posted : January 29, 2021
Sponsor:
Collaborator:
Cancer Insight, LLC
Information provided by (Responsible Party):
BriaCell Therapeutics Corporation

Tracking Information
First Submitted Date  ICMJE February 16, 2017
First Posted Date  ICMJE March 1, 2017
Results First Submitted Date  ICMJE December 10, 2019
Results First Posted Date  ICMJE January 29, 2021
Last Update Posted Date January 29, 2021
Actual Study Start Date  ICMJE May 5, 2017
Actual Primary Completion Date November 22, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2021)
Number of Patients With Treatment Emergent Adverse Events Occurring in Two or More Patients [Safety] [ Time Frame: Through study completion, an average of 1 year ]
To evaluate the number of patients with toxicity events while on SV-BR-1-GM, as defined by the Common Terminology Criteria for Adverse Events (CTCAE)
Original Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
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 BriaVax, as defined by CTCAE
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2021)
  • 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
  • Number of Participants With an Adverse Event Related to SV-BR-1-GM Administration [Safety] [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the number of participants with an adverse event related to SV-BR-1-GM administration, as defined by CTCAE
  • 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.
  • 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
  • Durability of Tumor Response [ Time Frame: Through study completion, an average of 1 year ]
    Durability of response, as defined as complete response (disappearance of all tumors), partial response (30% or greater reduction in the sum of diameters of target lesions (tumors) with stable disease in non-target lesions) or stable disease (less than 20% increase in the sum of diameters of target lesions with no new lesions appearing) by evaluating those patients eligible to complete the optional treatments from 9-12 months
Original Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • 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 BriaVax, as defined by CTCAE
  • Relationship of Adverse Events to BriaVax [Safety] [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the relationship of toxicity events, as defined by CTCAE, to BriaVax administration
  • 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 immune-related response criteria (irRC)
  • 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 irRC
  • 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
Current Other Pre-specified Outcome Measures
 (submitted: January 27, 2021)
  • 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
  • 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.
  • Weight [ Time Frame: Through study completion, an average of 1 year ]
    To measure changes in weight.
  • 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
  • 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
Original Other Pre-specified Outcome Measures
 (submitted: February 28, 2017)
  • Immune responses to vaccine [ Time Frame: Through study completion, an average of 1 year ]
    To assess immune responses to vaccine, and to recall antigens, if any, as measured by DTH skin tests and/or other immunological tests
  • 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.
  • Weight [ Time Frame: Through study completion, an average of 1 year ]
    To measure changes in weight.
  • 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
  • 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
 
Descriptive Information
Brief Title  ICMJE SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer
Official Title  ICMJE A Phase I/IIa Study of SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer Patients
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breastcancer
  • Breast Neoplasm
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Interventions:
  • Biological: SV-BR-1-GM
  • Drug: Cyclophosphamide
  • Biological: Interferon-alpha-2b
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 28, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 22, 2018
Actual Primary Completion Date November 22, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. 14. Patients who require systemic steroids at a dose equivalent of >10 mg/day of prednisone. Beta-blocker therapy, while not exclusionary, is discouraged and alternatives should be sought if possible. The beta-blocker might compromise use of epinephrine for the rare possibility of anaphylaxis. Anticoagulants must be approved by the Investigator with notification of the Sponsor.
    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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03066947
Other Study ID Numbers  ICMJE 0001
WRI-GEV-007 ( Other Identifier: BriaCell )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BriaCell Therapeutics Corporation
Study Sponsor  ICMJE BriaCell Therapeutics Corporation
Collaborators  ICMJE Cancer Insight, LLC
Investigators  ICMJE
Study Director: George E Peoples, MD, FACS Cancer Insight, LLC
PRS Account BriaCell Therapeutics Corporation
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP