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

NCT02018419 | Withdrawn Phase 1 DMC

• 1 other identifier: ITL-014-TACT-MBC
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• To determine the safety of increased frequency of dosing

  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.

  Window is defined as the time required receiving two doses of AlloStim IV push plus 28 days follow-up

Secondary Outcomes (2)

• Health-Related Quality of Life

  From enrollment to 90 days after last dose administration.

• Evaluate the anti-tumor effect of Allostim combined with cryoablation at the new proposed dose and frequency schedule.

  90 days after last dose administration

Other Outcomes (2)

• Immunological Response

  90 days after last dose administration

• Anti-Tumor Response

  90 days after last dose administration

Study Arms (3)

Dosing Schedule A

EXPERIMENTAL

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.

Biological: AlloStim; Procedure: Cryoablation

Dosing Schedule B

EXPERIMENTAL

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.

Biological: AlloStim; Procedure: Cryoablation

Dosing Schedule C

EXPERIMENTAL

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.

Biological: AlloStim; Procedure: Cryoablation

Interventions

AlloStim BIOLOGICAL

AlloStim is derived from the blood of normal blood donors and is intentionally mismatched to the recipient.

Also known as: InSituVax, Personalized anti-tumor vaccine

Dosing Schedule A; Dosing Schedule B; Dosing Schedule C

Cryoablation PROCEDURE

Percutaneous ablation of a single metastatic tumor lesion usually in liver or bone. The procedure is conducted under CT or ultrasound image-guidance.

Dosing Schedule A; Dosing Schedule B; Dosing Schedule C

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women w/ histologically/cytologically confirmed breast carcinoma
• Documented progressive metastatic disease not amenable to curative surgery/radiotherapy
• Age ≥18 and ≤70 years
• Prior treatments that included capecitabine and both an anthracycline and a taxane drug and resistant to taxane therapy
• ER+ patients: minimum cumulative dose of anthracycline (≥ 180 mg/m² of doxorubicin or ≥ 300 mg/m² of epirubicin) or resistance to anthracycline, capecitabine and anti-hormonal therapy
• 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/adjuvant setting
• Post-menopausal ER+ and/or PR+ must have received at least 2 lines of prior anti-estrogen therapy, which includes an aromatase inhibitor
• Her2+ patients: at least 1 Her2+ targeted regimen containing trastuzumab alone or with pertuzumab/lapatinib. Trastuzumab/pertuzumab must have been discontinued at least 4 weeks before treatment
• Prior radiation therapy completed \>4 weeks before treatment
• Measurable disease according to revised RECIST v.1.1 guidelines with at least 1 lesion deemed to be safely accessible for serial biopsy
• ECOG \<2
• Adequate hematological function
• Absolute granulocyte count ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• PT/INR ≤ 1.5

You may not qualify if:

• Peritoneal carcinomatosis
• Moderate-large ascites accumulation requiring/likely to require paracentesis
• Clinical/radiological evidence of brain metastasis/leptomeningeal involvement
• Pulmonary lymphangitis/symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment
• History of 2nd 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 with no evidence of recurrence
• \>3 prior chemotherapy regimens for metastatic disease
• History of severe hypersensitivity to monoclonal antibody drugs/any contraindication to study drugs
• Pregnant or breast feeding
• Any serious, concurrent uncontrolled medical disorder
• Prior hepatectomy, liver chemoembolization, liver cryoablation/ radiofrequency ablated
• Symptomatic pulmonary disease
• Bevacizumab (Avastin®) within 3 weeks of accrual
• Prior allogeneic bone marrow/stem cell or solid organ transplant
• Chronic use (\> 2 weeks) of greater than physiologic doses of corticosteroid agent (dose equivalent to \> 10 mg/day of prednisone) within 30 days of the first day of study treatment. Topical and inhaled corticosteroids are permitted
• Concomitant active autoimmune disease

Sponsors & Collaborators

• Mirror Biologics, Inc.: lead

Study Sites (1)

Medical Oncology Associates of San Diego

San Diego, California, 92123, United States

Location

Related Publications (5)

• Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.

  PMID: 18054441 RESULT

• Har-Noy M, Zeira M, Weiss L, Slavin S. Completely mismatched allogeneic CD3/CD28 cross-linked Th1 memory cells elicit anti-leukemia effects in unconditioned hosts without GVHD toxicity. Leuk Res. 2008 Dec;32(12):1903-13. doi: 10.1016/j.leukres.2008.05.007. Epub 2008 Jun 18.

  PMID: 18565579 RESULT

• Har-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009 Apr;33(4):525-38. doi: 10.1016/j.leukres.2008.08.017. Epub 2008 Oct 1.

  PMID: 18834631 RESULT

• Janikashvili N, LaCasse CJ, Larmonier C, Trad M, Herrell A, Bustamante S, Bonnotte B, Har-Noy M, Larmonier N, Katsanis E. Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia. Blood. 2011 Feb 3;117(5):1555-64. doi: 10.1182/blood-2010-06-288621. Epub 2010 Dec 1.

  PMID: 21123824 RESULT

• LaCasse CJ, Janikashvili N, Larmonier CB, Alizadeh D, Hanke N, Kartchner J, Situ E, Centuori S, Har-Noy M, Bonnotte B, Katsanis E, Larmonier N. Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-gamma-dependent mechanism. J Immunol. 2011 Dec 15;187(12):6310-7. doi: 10.4049/jimmunol.1101812. Epub 2011 Nov 9.

  PMID: 22075702 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cryosurgery

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Zivile Katiliene, Ph.D.

  Immunovative Clinical Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 23, 2013
• Study Start: March 1, 2014
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: January 22, 2020

Record last verified: 2015-04

Locations

US (1)