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Phase II/III, Randomized, Double Blind, Parallel Arm Study Comparing AlloStim Combined With Cryoablation to Placebo Combined With Cryoablation in Anthracycline, Taxane and Capecitabine Pre-Treated Metastatic Breast Cancer.

Phase 2/Phase 3
18 Years
70 Years
Not Enrolling
Metastatic Breast Cancer

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Trial Information

Phase II/III, Randomized, Double Blind, Parallel Arm Study Comparing AlloStim Combined With Cryoablation to Placebo Combined With Cryoablation in Anthracycline, Taxane and Capecitabine Pre-Treated Metastatic Breast Cancer.

Breast cancer is the most prevalent malignancy in women affecting more than 1 million women
a year and metastatic breast cancer (MBC) is a leading cause of mortality, accounting for
more than 400,000 deaths annually worldwide. Anthracycline- and taxane-containing regimens
have been established as the most effective chemotherapeutic agents for first- and
second-line therapies in MBC with respect to a prolongation of survival time. Because of
this, more women are receiving anthracyclines and taxanes early in the treatment of the
disease. Even despite this recent trend toward aggressive treatment of early stage breast
cancer with anthracyclines and taxanes, nearly half of these women will have metastatic
recurrence. The prior exposure to anthracycline and taxane drugs leaves women facing
first-line therapy for metastatic recurrent disease resistant to anthracycline and taxane
drugs and, thus, with limited treatment options. US FDA currently approved ixabepilone
(Ixempra) and Havalan (Eribulin) in this setting, but these drugs have not been shown to
provide a survival advantage compared to capecitabine (Xeloda). However, only approximately
25% of MBC patients respond to capecitabine. In addition, these approved drugs and other
chemotherapy drug options have significant toxicity profiles. Accordingly, there is a need
for new effective treatments for women with MBC that have been previously pre-treated with
taxane, anthracycline and capecitabine. This study is designed to determine if AlloStim will
provide a survival benefit to these woman.

Resistance to anthracycline and taxane is defined clinically as disease recurrence within 6
months of completion of adjuvant or neoadjuvant treatment with these agents or tumor
progression that occurs during treatment or within 3 months of the last dose of treatment.

Inclusion Criteria:

- Women with histologically or cytologically confirmed carcinoma of the breast.

- Documented progressive metastatic disease not amenable to curative surgery or

- Age ≥18 and ≤70 years

- Patients must have prior treatments that have included capecitabine and both an
anthracycline and a taxane drug and must be resistant to taxane therapy.

- 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+

- 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.

- Post-menopausal ER+ and/or PR+ patients must have received at least two lines of
prior anti-estrogen therapy, which includes an aromatase inhibitor.

- 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 randomization.

- Prior radiation therapy must be completed at least 4 weeks before randomization.

- Measurable disease according to revised RECIST v.1.1 guidelines with at least one
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

- 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.

- Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)

- Adequate organ function.

- Creatinine ≤ 1.5 mg/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times normal if liver involvement)

- Aspartate aminotransferase (AST) or (SGOT) ≤ 5.0 times ULN

- Alanine aminotransferase (ALT) or (SGPT) ≤ 5.0 times ULN

- EKG without clinically relevant abnormalities

- Pre-menopausal patients with child bearing potential must agree to use adequate

- Study specific informed consent in the native language of the subject.

Exclusion Criteria:

- Peritoneal carcinomatosis

- Moderate to large ascites accumulation requiring or likely to require paracentesis

- Clinical evidence or radiological evidence of brain metastasis or leptomeningeal

- Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in
pulmonary dysfunction requiring active treatment.

- 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

- Patients having received > 3 regimens of prior chemotherapy for metastatic disease

- History of severe hypersensitivity to monoclonal antibody drugs or any
contraindication to any of the study drugs.

- Pregnant or breast feeding

- Patients who have any serious, concurrent uncontrolled medical disorder

- Prior hepatectomy, liver chemoembolization, liver cryoablation or RFA

- 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 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

- Concomitant active autoimmune disease (e.g., rheumatoid arthritis, multiple
sclerosis, autoimmune thyroid disease, uveitis)

- Prior experimental therapy or cancer vaccine treatment (e.g., dendritic cell therapy,
heat shock vaccine)

- Current immunosuppressive therapy, including: cyclosporine, antithymocyte globulin,
or tacrolimus within 1 month of study entry.

- History of blood transfusion reactions

- Known allergy to bovine products

- Know allergy to murine products

- 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

- Cardiac disease of symptomatic nature or cardiac ejection fraction < 45%

- History of HIV positivity or AIDS

- Psychiatric or addictive disorders or other condition that, in the opinion of the
investigator, would preclude study participation

- 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/RFA procedure.

- Use of low molecular weight heparin preparations unless can be discontinued 8 hours
prior to cryoablation or RFA.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Overall Survival

Outcome Description:

To assess whether cryoablation combined with AlloStim treatment (arm 1) provides an overall survival (OS) advantage when compared to treatment with cryoablation combined with placebo (arm 2).

Outcome Time Frame:

the ITT population from randomization within 30 days of accrual to death for any cause followed for up to 2 years from date of randomization

Safety Issue:


Principal Investigator

Wirote Lausoontornsiri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute of Thailand


Thailand: Ministry of Public Health

Study ID:




Start Date:

April 2013

Completion Date:

April 2016

Related Keywords:

  • Metastatic Breast Cancer
  • cancer vaccine
  • AlloStim
  • Immunovative
  • Immunotherapy
  • Allogeneic cell therapy
  • cryoablation
  • Breast Neoplasms