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Rollover Study of SV-BR-1-GM in Combination With Ipilimumab or Pembrolizumab

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ClinicalTrials.gov Identifier: NCT03328026
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : September 11, 2018
Sponsor:
Collaborator:
Cancer Insight, LLC
Information provided by (Responsible Party):
BriaCell Therapeutics Corporation

Brief Summary:
This is an open-label study of Study WRI-GEV-007, which evaluates SV-BR-1-GM in metastatic or locally recurrent breast cancer patients, in combination with pembrolizumab (Keytruda) or ipilimumab (Yervoy). Patients who with advanced breast cancer who have failed prior therapies will be eligible to enroll in this study. The study will evaluate SV-BR-1-GM in combination with pembrolizumab (Keytruda) if their tumors express PD-L1 or PD-L2, or in combination with ipilimumab (Yervoy) if their tumors do not express PD-L1 or PD-L2. Treatment cycles will be every 3 weeks with evaluations for tumor progression or response every 6-12 weeks.

Condition or disease Intervention/treatment Phase
Breast Cancer Female Breast Neoplasm Female Biological: SV-BR-1-GM Biological: Pembrolizumab Biological: Ipilimumab Drug: Low dose cyclophosphamide Biological: Interferon Inoculation Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa Rollover Study of the Whole-Cell Vaccine SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer Patients in Combination With Ipilimumab or Pembrolizumab
Actual Study Start Date : March 16, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Pembrolizumab SV-BR-1-GM combination
Patients with tumors that express PD-L1 or PD-L2 will be treated with the SV-BR-1-GM regimen (including pre-treatment with low dose cyclophosphamide and post-treatment Interferon inoculation) in combination with pembrolizumab with cycles every 3 weeks
Biological: SV-BR-1-GM
SV-BR-1-GM inoculation intradermally in 4 sites on the upper back (x2) and thighs (x2).

Biological: Pembrolizumab
Pembrolizumab will be given 200 mg intravenously either ~2 or ~4 days after SV-BR-1-GM inoculation for up to 24 infusions. Cycles will be every 3 weeks.
Other Name: Keytruda

Drug: Low dose cyclophosphamide
Pretreatment with low dose cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation.
Other Name: Cytoxan

Biological: Interferon Inoculation
Post-inoculation low dose Interferon-alpha-2b into the vaccination sites ~2 and ~4 days after SV-BR-1-GM inoculation.
Other Name: Intron A

Experimental: Ipilimumab SV-BR-1-GM combination
Patients with tumors that do not express PD-L1 or PD-L2 will be treated with the SV-BR-1-GM regimen (including pre-treatment with low dose cyclophosphamide and post-treatment Interferon inoculation) in combination with ipilimumab with cycles every 3 weeks
Biological: SV-BR-1-GM
SV-BR-1-GM inoculation intradermally in 4 sites on the upper back (x2) and thighs (x2).

Biological: Ipilimumab
Ipilimumab will be given 3 mg/kg intravenously either ~2 or ~4 days after SV-BR-1-GM inoculation for up to 4 infusions. Cycles will be every 3 weeks.
Other Name: Yervoy

Drug: Low dose cyclophosphamide
Pretreatment with low dose cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation.
Other Name: Cytoxan

Biological: Interferon Inoculation
Post-inoculation low dose Interferon-alpha-2b into the vaccination sites ~2 and ~4 days after SV-BR-1-GM inoculation.
Other Name: Intron A




Primary Outcome Measures :
  1. Evaluate the Safety of SV-BR-1-GM (Adverse Events) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [Safety] [ Time Frame: Through study completion, an average of 1 year ]

    To evaluate the safety of SV-BR-1-GM as assessed by:

    o Adverse Events (AEs), including Serious Adverse Events (SAEs)



Secondary Outcome Measures :
  1. Evaluate the Safety of SV-BR-1-GM (Laboratory Parameters) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [Safety] [ Time Frame: Through study completion, an average of 1 year ]

    To evaluate the safety of SV-BR-1-GM as assessed by:

    o Safety Laboratory Parameters


  2. Evaluate the tumor response to SV-BR-1-GM (ORR) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Tumor response as assessed by:

    o Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per immune-related response criteria (iRECIST)


  3. Evaluate the tumor response to SV-BR-1-GM (Non-progression) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Tumor response as assessed by:

    o Non-progressive rate, defined as CR, PR or stable disease (SD) per iRECIST


  4. Evaluate the tumor response to SV-BR-1-GM (Durability of response) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Tumor response as assessed by:

    o Durability of response, by evaluating those patients eligible to complete the optional treatments from 9-12 months


  5. Evaluate the immune responses elicited by SV-BR-1-GM (DTH) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Immune responses as assessed by:

    o Delayed type hypersensitivity (DTH) skin tests


  6. Evaluate the immune responses elicited by SV-BR-1-GM (T cell responses) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Immune responses as assessed by:

    o T cell responses to SV-BR-1


  7. Evaluate the immune responses elicited by SV-BR-1-GM (other immunological tests) when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Immune responses as assessed by:

    o Other immunological tests


  8. Evaluate patient characteristics (HLA type) that may be predictive of responses to SV-BR-1-GM when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Patient characteristics including:

    o Human Leukocyte Antigen (HLA) type


  9. Evaluate tumor characteristics that may be predictive of responses to SV-BR-1-GM when administered in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]

    Patient and tumor characteristics including:

    o Tumor expression of PD-L1, PD-L2 and cancer/testis antigens such as PRAME


  10. Evaluate Quality of Life (QOL) in patients administered SV-BR-1-GM in combination with ipilimumab (for patients with PD-L1/2- tumors) or pembrolizumab (for patients with PD-L1/2+ tumors) [ Time Frame: Through study completion, an average of 1 year ]
    Quality of Life as assessed by the Short Form 36 (SF36)



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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:

  1. Have histological confirmation of breast cancer with recurrent and/or metastatic lesions via investigational site which has failed prior therapy.

    • Patients with persistent disease and local recurrence must not be amenable to local treatment.
    • For patients with metastatic disease:

      • Human epidermal growth factor 2 (HER2) positive and estrogen receptor (ER) or progesterone receptor (PR) positive tumors: must be refractory to hormonal therapy (e.g., aromatase inhibitor, tamoxifen or fluvestrant) and previously treated with at least 2 regimens including at least two anti-HER2 agents (e.g., trastuzumab and pertuzumab).
      • HER2 negative and either ER or PR positive tumors: must be refractory to hormonal therapy (e.g. aromatase inhibitor, tamoxifen or fluvestrant) and previously treated with at least 2 chemotherapy containing regimens.
      • HER2 positive and ER and PR negative tumors: must have failed at least 2 regimens including at least two anti-HER2 agents (e.g., trastuzumab and pertuzumab).
      • Triple Negative tumors: Must have exhausted other available therapies including prior treatment with a taxane and carboplatin.

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

    1. Must have received prior radiation therapy for brain metastases or be ineligible for radiation therapy
    2. There is no need for steroids and patients have not had steroids for at least 2 weeks
    3. No individual tumor size is >50 mm
    4. ECOG status <3
    5. Tumor is not impinging on Middle Cerebral Artery/speech-motor strip
    6. If surgically debulked, must be healed from surgery and at least 3 weeks have elapsed since general anesthesia
    7. 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. Have provided written informed consent

Exclusion Criteria:

  1. Concurrent or recent chemotherapy, radiotherapy, immunotherapy (except the SV-BR-1-GM regimen), 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 the designated combination immunotherapy, GM-CSF, Interferon-alpha-2b (Merck), yeast, beef, or to any components used in the preparation of SV-BR-1-GM.
  3. History of clinical hypersensitivity to the immunotherapy proposed for combination treatment.
  4. BUN >30 in conjunction with a creatinine >2.
  5. Absolute granulocyte count < 1000; platelets <100,000.
  6. Bilirubin >2.0; alkaline phosphatase >5x upper limit of normal (ULN); ALT/AST >2x ULN. For patients with hepatic metastases, ALT/AST >5x ULN is exclusionary.
  7. Proteinuria >1+ on urinalysis or >1 gm/24hr.
  8. 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.
  9. New York Heart Association stage 3 or 4 cardiac disease.
  10. A pleural or pericardial effusion of moderate severity or worse.
  11. Any woman of childbearing potential (i.e., has had a menstrual cycle within the past year and has not been surgically sterilized), unless she: agrees to take appropriate precautions to avoid becoming pregnant (with at least 99% certainty) during the study and has a negative serum pregnancy test within 7 days prior to starting treatment.
  12. Women who are pregnant or nursing.
  13. 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.
  14. Patients who are HIV positive (by self-report) or have clinical or laboratory features indicative of AIDS.
  15. Patients who require systemic steroids at doses >10 mg daily of prednisone or equivalent or any immunosuppressive drugs. 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.
  16. Patients who are on treatment for an autoimmune disease, unless specifically approved by the Investigator and the Sponsor.
  17. Patients with a history of colitis.
  18. Patients with severe psychiatric (e.g., schizophrenia, bipolar, or borderline personality disorder) or other clinically progressive major medical problems, unless approved by the Investigator.
  19. Male breast cancer patients.
  20. Patients may not be on a concurrent clinical trial, unless approved by Investigator.

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): NCT03328026


Contacts
Contact: Karen Arrington, RN BSN CCRP 210-243-5711 karrington@cancerinsight.com
Contact: George E Peoples, MD, FACS 210.557.4291 gpeoples@cancerinsight.com

Locations
United States, California
St. Joseph Heritage Healthcare Recruiting
Santa Rosa, California, United States, 95403
Contact: Jennafer Carlin-Rosset, MPH    707-521-3830    Jennafer.Carlin@stjoe.org   
Contact: Kim Young, RN, CCRC    707-521-3830    Kimberly.Young@stjoe.org   
Principal Investigator: Jarrod P Holmes, M.D.         
United States, Florida
University of Miami/Sylvester at Plantation Recruiting
Plantation, Florida, United States, 33324
Contact: Deborah M Conte, CCRC    954-210-1171    dmc238@med.miami.edu   
Principal Investigator: Carmen J Calfa, MD         
United States, Kansas
Cancer Center of Kansas (CCK) Recruiting
Wichita, Kansas, United States, 67214
Contact: Susan Davis, RN, BSN    316-613-4318    susan.davis@cancercenterofkansas.com   
Contact: Julie Hintz    316-613-4317    julie.hintz@cancercenterofkansas.com   
Principal Investigator: Shaker Dakhil, MD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Rita Murphy, MA, MPH    215-955-9626    rita.murphy@jefferson.edu   
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    rachel.macomber@providence.org   
Contact: Katie Lyon    425-297-5532    katie.lyon@providence.org   
Principal Investigator: Jason Lukas, MD, PhD         
Sponsors and Collaborators
BriaCell Therapeutics Corporation
Cancer Insight, LLC
Investigators
Study Director: George E Peoples, MD, FACS Cancer Insight, LLC

Additional Information:
Responsible Party: BriaCell Therapeutics Corporation
ClinicalTrials.gov Identifier: NCT03328026     History of Changes
Other Study ID Numbers: BRI-ROL-001
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: September 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
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Pembrolizumab
Interferons
Antibodies, Monoclonal
Vaccines
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