Increased Frequency of AlloStim(TM) Dosing in Combination With Cryoablation in Metastatic Breast Cancer Patients (MBC)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by Immunovative Therapies, Ltd.
Sponsor:
Information provided by (Responsible Party):
Immunovative Therapies, Ltd.
ClinicalTrials.gov Identifier:
NCT02018419
First received: December 17, 2013
Last updated: NA
Last verified: December 2013
History: No changes posted

December 17, 2013
December 17, 2013
March 2014
March 2016   (final data collection date for primary outcome measure)
  • To determine the safety of increased frequency of dosing [ Time Frame: Window is defined as the time required receiving two doses of AlloStim IV push plus 28 days follow-up ] [ Designated as safety issue: Yes ]
    Three patients are enrolled at each frequency schedule in the absence of dose limiting toxicity (DLT). A DLT is defined as any allergic or autoimmune toxicity or other study drug related toxicity Grade 3 or higher during the DLT assessment window.
  • Evaluate the anti-tumor effect of Allostim combined with cryoablation at the new proposed dose and frequency schedule. [ Time Frame: 90 days after last dose administration ] [ Designated as safety issue: No ]
    Each treatment schedule will be monitored for radiological, pathological, and immunological response. These assessments will be compared between three treatment schedules.
Same as current
No Changes Posted
Health-Related Quality of Life [ Time Frame: From enrollment to 90 days after last dose administration. ] [ Designated as safety issue: No ]
Health-Related Quality of life will be measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and its supplementary breast cancer questionnaire (QLQ-BR23).
Same as current
  • Immunological Response [ Time Frame: 90 days after last dose administration ] [ Designated as safety issue: No ]
    Blood samples will be evaluated for immunological response and a determination made as to whether immunological response correlates with RECIST and pathology.
  • Anti-Tumor Response [ Time Frame: 90 days after last dose administration ] [ Designated as safety issue: No ]
    The changes in tumor burden by RECIST and compare these changes with the pathological analysis of corresponding biopsies.
Same as current
 
Increased Frequency of AlloStim(TM) Dosing in Combination With Cryoablation in Metastatic Breast Cancer Patients
In-Situ Cancer Vaccine: Phase I/IIb, Open-Label Study to Assess Safety of AllostimTM in Combination With Cryoablation in Metastatic Breast Cancer Previously Treated With an Anthracycline, a Taxane and Capecitabine

This phase I/II study is designed to compare different treatment schedules of a personalized anti-cancer vaccine protocol which combines the cryoablation of a selected metastatic lesion with intra-tumor immunotherapy. The cryoablation causes the tumor to release tumor-specific antigens into the surrounding environment. The injection of bioengineered allogeneic immune cells, AlloStim(TM), into the lesion is designed to modulate the immune response and educate the immune system to kill other tumor cells.

The study will assess three different dosing schedules. A standard 3 plus 3 study design will be used. The starting dose for each dosing schedule will be escalated in subsequent groups of patients. The study will evaluate safety of increased frequency of AlloStim (TM) dosing and anti-tumor effect of the new proposed dose and frequency schedule.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Breast Cancer
  • Biological: AlloStim
    AlloStim is derived from the blood of normal blood donors and is intentionally mismatched to the recipient.
    Other Names:
    • InSituVax
    • Personalized anti-tumor vaccine
  • Procedure: Cryoablation
    Percutaneous ablation of a single metastatic tumor lesion usually in liver or bone. The procedure is conducted under CT or ultrasound image-guidance.
  • Experimental: Dosing Schedule A
    1. the priming step with ID injection of AlloStim on Days 0, 7, and 14;
    2. the ablation step with cryoablation and intra-tumor injection of AlloStim on Day 21;
    3. the activation step with an IV infusion of AlloStim on Day 28;
    4. the booster step with intravenous booster infusion of AlloStim on Days 56 and 84;

    Protocol follow-up procedures continue until day 168 and at investigator discretion thereafter.

    Interventions:
    • Biological: AlloStim
    • Procedure: Cryoablation
  • Experimental: Dosing Schedule B
    1. the priming step with ID injection of AlloStim on Days 0 and 3 and an additional ID injection of AlloStim on Days 7 and 10;
    2. the ablation step with cryoablation and intra-tumor injection of AlloStim on Day 14;
    3. the activation step with an IV infusion of AlloStim on Day 21;
    4. the booster step with intravenous booster infusion of AlloStim on Days 49 and 77.

    Protocol follow-up procedures continue until day 168 and at investigator discretion thereafter.

    Interventions:
    • Biological: AlloStim
    • Procedure: Cryoablation
  • Experimental: Dosing Schedule C
    1. the priming step with ID injection of AlloStim on Days 0 and 3 and an additional ID injection of AlloStim on Days 7 and 10;
    2. the ablation step with cryoablation and intra-tumor injection of AlloStim on Day 14, and intra-tumor injection of AlloStim again into the same cryoablated lesion on Day 17;
    3. the activation step with an IV infusion of AlloStim on Day 21;
    4. the booster step with intravenous infusion of AlloStim on days 49 and 77.

    Protocol follow-up procedures continue until day 168 and at investigator discretion thereafter.

    Interventions:
    • Biological: AlloStim
    • Procedure: Cryoablation

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
31
March 2017
March 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Women with histologically or cytologically confirmed carcinoma of the breast.
  2. Documented progressive metastatic disease not amenable to curative surgery or radiotherapy.
  3. Age ≥18 and ≤70 years
  4. Patients must have prior treatments that have included capecitabine and both an anthracycline and a taxane drug and must be resistant to taxane therapy.

    1. Patients must have received a minimum cumulative dose of anthracycline (≥ 180 mg/m² of doxorubicin or ≥ 300 mg/m² of epirubicin) or be resistant to an anthracycline and resistant to capecitabine and anti-hormonal therapy (ER+ patients).
    2. Resistance is defined as tumor progression while receiving treatment or progression within 4 months of the last dose in the metastatic setting, or recurrence within 12 months in the neoadjuvant or adjuvant setting.
  5. Post-menopausal ER+ and/or PR+ patients must have received at least two lines of prior anti-estrogen therapy, which includes an aromatase inhibitor.
  6. Her2+ patients must have received at least one Her2+ targeted regimen containing trastuzumab alone or with pertuzumab or with lapatinib. Patients who have been treated with trastuzumab or pertuzumab must have discontinued therapy at least 4 weeks prior to study treatment.
  7. Prior radiation therapy must be completed at least 4 weeks before treatment.
  8. Measurable disease according to revised RECIST v.1.1 guidelines with at least one lesion deemed to be safely accessible for serial biopsy.
  9. ECOG <2
  10. Adequate hematological function

    1. Absolute granulocyte count ≥ 1,500/mm3
    2. Platelet count ≥ 100,000/mm3
    3. PT/INR ≤ 1.5
    4. INR correctable to ≤ 1.5 or a PT/PTT correctable to normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be monitored weekly prior to any intervention to assure INR is stable. However, heparin or warfarin must be withheld prior to biopsy such that the above criteria are met.
    5. Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)
  11. Adequate organ function.

    1. Creatinine ≤ 1.5 mg/dL
    2. Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
    3. Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times normal if liver involvement)
    4. Aspartate aminotransferase (AST) or (SGOT) ≤ 5.0 times ULN
    5. Alanine aminotransferase (ALT) or (SGPT) ≤ 5.0 times ULN
  12. EKG without clinically relevant abnormalities
  13. Pre-menopausal patients with child bearing potential must agree to use adequate contraception.
  14. Study specific informed consent in the native language of the subject.

Exclusion Criteria:

  1. Peritoneal carcinomatosis.
  2. Moderate to large ascites accumulation requiring or likely to require paracentesis.
  3. Clinical evidence or radiological evidence of brain metastasis or leptomeningeal involvement.
  4. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment.
  5. History of second primary malignancy, except: bilateral breast carcinoma, in situ carcinoma of the cervix, adequately treated non-melanomatous carcinoma of the skin, and other malignancy treated at least 5 years previously with no evidence of recurrence.
  6. Patients having received > 3 regimens of prior chemotherapy for metastatic disease.
  7. History of severe hypersensitivity to monoclonal antibody drugs or any contraindication to any of the study drugs.
  8. Pregnant or breast feeding.
  9. Patients who have any serious, concurrent uncontrolled medical disorder.
  10. Prior hepatectomy, liver chemoembolization, liver cryoablation or radiofrequency ablated.
  11. Symptomatic pulmonary disease.
  12. Bevacizumab (Avastin®) within 3 weeks of accrual.
  13. Prior allogeneic bone marrow/stem cell or solid organ transplant.
  14. Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to > 10 mg/day of prednisone) within 30 days of the first day of investigational product treatment.

    - Topical and inhaled corticosteroids are permitted

  15. Concomitant active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis).
  16. Prior experimental therapy or cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine).
  17. Current immunosuppressive therapy, including: cyclosporine, antithymocyte globulin, or tacrolimus within 1 month of study entry.
  18. History of blood transfusion reactions.
  19. Known allergy to bovine products.
  20. Know allergy to murine products.
  21. Progressive viral or bacterial infection

    - All infections must be resolved and the patient must remain afebrile for seven days without antibiotics prior to being placed into the study

  22. Cardiac disease of symptomatic nature or cardiac ejection fraction < 45%.
  23. History of HIV positivity or AIDS.
  24. Psychiatric or addictive disorders or other condition that, in the opinion of the investigator, would preclude study participation.
  25. Concurrent medication known to interfere with platelet function or coagulation (e.g., aspirin, ibuprofen, clopidogrel, or warfarin) unless such medications can be discontinued for an appropriate time period based on the drug half-life and known activity (e.g., aspirin for 7 days) prior to cryoablation procedure.
  26. Use of low molecular weight heparin preparations unless can be discontinued 8 hours prior to cryoablation.
Female
18 Years to 70 Years
No
Contact: Zivile Katiliene, Ph.D. 1-760-444-9040 zivile@immunovative.co.il
Contact: Thu Bui, B.S. 1-760-444-9040 thu@immunovative.co.il
United States
 
NCT02018419
ITL-014-TACT-MBC
Yes
Immunovative Therapies, Ltd.
Immunovative Therapies, Ltd.
Not Provided
Study Director: Zivile Katiliene, Ph.D. Immunovative Clinical Research
Immunovative Therapies, Ltd.
December 2013

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