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A Phase I Trial of An Admixture of Recombinant Vaccinia Virus That Express DF3/MUC1 and rV-TRICOM (B7.ICAM-1, and LFA-3) in Patients With Metastatic Adenocarcinoma of The Breast

Phase 1
18 Years
Not Enrolling
Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

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Trial Information

A Phase I Trial of An Admixture of Recombinant Vaccinia Virus That Express DF3/MUC1 and rV-TRICOM (B7.ICAM-1, and LFA-3) in Patients With Metastatic Adenocarcinoma of The Breast


I. To assess the toxicity associated with repeated vaccination with an admixture of
recombinant vaccinia viruses (rV-MUC-1 and rV-TRICOM).

II. To determine the maximum tolerated dose (MTD) of rV-MUC-1 and rV-TRICOM vaccine

III. To evaluate the toxicity of adding GM-CSF to the admixture of the rV-MUC-1 and


I. To assess host immune reactivity following rV-MUC-1 and rV-TRICOM with and without GM-CSF

II. To determine whether vaccination with rV-MUC-1 and rV-TRICOM with and without GM-CSF is
associated with antitumor activity.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive vaccination comprising recombinant vaccinia-MUC-1 and recombinant
vaccinia-TRICOM vaccine intradermally on days 1 and 29 (for a total of 2 doses) in the
absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of recombinant vaccinia-MUC-1 and
recombinant vaccinia-TRICOM vaccine until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience
dose-limiting toxicity. Once the MTD is determined, an additional 10 patients (including 5
HLA-A2-positive patients) receive vaccination as above at the MTD and sargramostim (GM-CSF)
subcutaneously on days 1-4 and 29-32.

Patients are followed at 4 weeks, monthly until disease progression, and then annually for
up to 15 years.

PROJECTED ACCRUAL: A total of 11-22 patients will be accrued for this study within 18-24

Inclusion Criteria:

- Subjects must have a histologically confirmed diagnosis of metastatic carcinoma of
the breast; measurable disease is not required; subjects who are NED are eligible;
subjects must have had at least one prior regimen of chemotherapy, immunotherapy, or
hormonal therapy prior to entering this study; subjects may have received any number
of prior therapies for metastatic disease

- Subjects must have an ECOG performance status of 0-1

- WBC > 2000/mm^3

- Platelet count > 100,000/mm^3

- Serum creatinine =< 2.0 mg/dl

- Serum bilirubin =< 1.5 mg/dl

- SGPT < 3 times the upper limit of normal

- >= 4 weeks since chemotherapy (>= 6 weeks for nitrosoureas or mitomycin C), hormonal
therapy or radiation therapy; subjects must have recovered from all acute toxicity
associated with the prior regimen; subjects receiving concurrent hormonal treatment
or local radiation are not eligible

- Subjects must be HLA typed if not already previously done (5/10 subjects at the MTD
dose level must be HLA A2 positive)

- Subjects must not have clinical evidence of altered immune responsiveness or
autoimmune syndromes (scleroderma, systemic lupus erythematosus, etc.); subjects must
be HIV antibody negative; this treatment may be associated with increased adverse
effects for individuals with immune deficiencies, and HIV-associated symptoms
preclude accurate assessment of toxicity

- Subjects must not have undergone splenectomy

- The recombinant vaccinia vaccine should not be administered if the following apply to
either recipients or, for at least three weeks after vaccination, their close
household contacts: persons with active or a history of extensive eczema or other
eczematoid skin disorders; those with other acute, chronic or exfoliative skin
conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne
or other open rashes or wounds) until condition resolves; pregnant or nursing women;
children under 5 years of age; and immunodeficient or immunosuppressed persons (by
disease or therapy), including HIV infection; close household contacts are those who
share housing or have close physical contact; determination of the severity of these
conditions will be made by the investigator or co-investigator

- Subjects must not have any other serious medical condition that in the opinion of the
investigator is incompatible with the protocol; subjects with active infections
requiring antibiotics are not eligible until the infection has cleared and the
antibiotics have been stopped for at least 3 days

- Subjects must have had prior vaccinia (smallpox) exposure, determined by subject
history, medical documentation, or scar characteristic of vaccinia exposure; there
must be no history of allergy or untoward reaction to prior vaccinia (smallpox)

- Tumor tissue positive for staining with MAbs DF3 and/or DF3-P or elevated serum
CA15-3 (also known as CA27-29); note: this can be done on stored slides, but subject
will be responsible for costs if not covered by insurance

- Subjects must not have a history of seizures, encephalitis or multiple sclerosis

- Subjects must not be allergic to eggs

- Women of child-bearing potential must agree to use highly effective contraception or
abstinence prior to study entry and for at least 4 weeks after the last vaccination;
women who are breast-feeding are not eligible for this study; should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately

- Signed informed consent

- Participants who have been previously treated with vaccinia vectors or MUC1 such as
those on protocol T98-0057 (DFPCC # 97-050) are not eligible for this study

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD defined as the dose level preceding the dose in which 2 out of 6 patients experience dose limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria version 2.0

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Joseph Eder

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

October 2003

Completion Date:

Related Keywords:

  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Vaccinia
  • Breast Neoplasms, Male



Dana-Farber Cancer Institute Boston, Massachusetts  02115