Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2/Neu-Overexpressing Metastatic Breast Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 17 December 2012
• Main ID: NCT00399529
• Date of registration: 13/11/2006
• Primary sponsor: Sidney Kimmel Comprehensive Cancer Center
• Public title: Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2/Neu-Overexpressing Metastatic Breast Cancer
• Scientific title: A Feasibility Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2/Neu-Overexpressing Metastatic Breast Cancer.
• Date of first enrolment: September 2006
• Target sample size: 22
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00399529
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Leisha A Emens, M.D.,Ph.D.
• Affiliation: Johns Hopkins University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients with histologically confirmed HER-2/neu-overexpressing adenocarcinoma of the
breast; this is defined as HER-2+ by IHC 3+ staining or FISH+. Prior adjuvant
Trastuzumab therapy is permitted. Patients must not be eligible for therapy of known
curative potential for metastatic breast cancer if it is identified during the course
of the study.

2. Patients may have measurable or evaluable disease.

3. Stable CNS disease that has been adequately treated and is not under active treatment
allowed.

4. Age 18 years or older.

5. Able to give informed consent.

6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or
1.

7. No systemic oral steroids administered within 28 days prior to initiating treatment
on protocol. Topical, ocular, and nasal steroids are allowed, as are those applied to
mucus membranes.

8. No prior or currently active autoimmune disease requiring management with systemic
immunosuppression. This includes inflammatory bowel disease, systemic vasculitis,
scleroderma, psoriasis, multiple sclerosis, hemolytic anemia or immune-mediated
thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's
syndrome, sarcoidosis, or other rheumatologic disease. Asthma or chronic obstructive
pulmonary disease that does not require daily systemic corticosteroids is acceptable.

9. Not pregnant, and on appropriate birth control if of child-bearing potential.

10. No history of other malignancies within the prior five years (excluding a history of
carcinoma in situ of the cervix, superficial non-melanoma skin cancer, and
superficial bladder cancer).

11. Adequate bone marrow reserve with ANC > 1000 and platelets > 100,000.

12. Adequate renal function with serum creatinine < 2.0.

13. Adequate hepatic reserve with serum bilirubin < 2.0, AST/ALT < 2X the upper limit of
normal, and alkaline phosphatase < 5X the upper limit of normal. Serum bilirubin >
2.0 is acceptable in the setting of known Gilbert's syndrome.

14. Adequate cardiac reserve with a cardiac ejection fraction within the lower limit of
facility normal by MUGA, or 45% by echocardiogram.

15. No active major medical or psychosocial problems that could be complicated by study
participation.

16. HIV negative.

Exclusion Criteria:

1. No histologic documentation of breast adenocarcinoma.

2. Breast adenocarcinoma that is not amplified for HER-2/neu gene expression by at least
2-fold by FISH analysis, or that is less than IHC 3+ when FISH negative.

3. Cardiac dysfunction documented by an ejection fraction less than the lower limit of
the facility normal by multi-gated acquisition (MUGA) scan, or 45% by
echocardiogram.

4. Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
resulting in dyspnea at rest.

5. History of autoimmune disease as detailed above.

6. Systemic oral corticosteroid treatment within 28 days prior to initiating treatment
on study.

7. Uncontrolled medical problems.

8. Evidence of active acute or chronic infection.

9. Chemotherapy, radiation therapy, or biologic therapy (except Trastuzumab) within 28
days prior to initiating treatment on study. Hormonal therapy and supportive therapy
with bisphosphonates will be allowed.

10. Participation in an investigational new drug trial within 28 days prior to initiating
treatment on study.

11. Pregnant or breast feeding.

12. Hepatic, renal, or bone marrow dysfunction as detailed above.

13. Concurrent malignancy or history of other malignancy within the last five years
except as noted above.

14. Corn allergy.

15. Known severe hypersensitivity to Trastuzumab (excluding mild to moderate infusion
reactions that are easily managed and do not recur).



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Breast Neoplasms

Intervention(s)

Biological: Allogeneic GM-CSF-secreting breast cancer vaccine

Drug: Cyclophosphamide

Drug: Trastuzumab

Primary Outcome(s)

Clinical benefit will be assessed by re-evaluating disease status with tumor markers and RECIST criteria, or with full evaluation upon the development of new symptoms. [Time Frame: Until 30 days after intervention]

Safety will be evaluated by assessing toxicity related to the vaccine, CY, Trastuzumab, cardiac dysfunction, and the potential induction of autoimmunity. [Time Frame: Until 30 days after intervention]

Secondary Outcome(s)

Immunological response [Time Frame: Until 30 days after intervention]

Secondary ID(s)

J05118

RAC 0605-778

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

American Cancer Society, Inc.

Avon Foundation

Cancer Treatment Research Foundation

Department of Defense

Genentech

The Commonwealth Fund