Know Cancer

or
forgot password

A Randomized Pilot Phase II Study of Docetaxel Alone or in Combination With PANVAC(Trademark)-V (Vaccinia) and PANVAC(Trademark)-F (Fowlpox) in Adults With Metastatic Breast Cancer


Phase 2
18 Years
85 Years
Open (Enrolling)
Both
Breast Cancer

Thank you

Trial Information

A Randomized Pilot Phase II Study of Docetaxel Alone or in Combination With PANVAC(Trademark)-V (Vaccinia) and PANVAC(Trademark)-F (Fowlpox) in Adults With Metastatic Breast Cancer


Background:

Weekly docetaxel therapy is currently used as a standard treatment for patients with
metastatic breast cancer.

Although many patients initially respond to this form of therapy, the majority will
eventually develop disease progression and die from their disease.

We have explored the use of combining pox vector vaccines with docetaxel. In a recent
clinical trial, men with prostate cancer were given both the vaccine and docetaxel without
any significant toxicity and the docetaxel did not diminish immune responses to the vaccine.

Objectives:

To evaluate progression free survival comparing PANVAC + docetaxel vs. docetaxel alone in
patients with metastatic breast cancer.

To evaluate overall survival comparing PANVAC + docetaxel vs. docetaxel alone in patients
with metastatic breast cancer.

To evaluate in both arms cluster of differentiation 8 (CD8+) T cell responses directed
against carcinoembryonic antigen (CEA) and mucin (MUC-1) in human leukocyte antigen 2
(HLA-A2), A3, and A24 positive patients by interferon-gamma enzyme linked immunosorbent spot
(ELISPOT) assay.

Eligibility:

Metastatic breast cancer (either male or female) with evidence of metastatic disease (must
have radiographic evidence of disease) and life expectancy of at least 4 months.

Patients may have received unlimited prior hormonal therapy or chemotherapy, but no prior
docetaxel for metastatic disease.

Hematological eligibility parameters within 16 days of starting therapy:

Granulocyte count greater than or equal to 1,500/mm^3, Platelet count greater than or equal
to 100,000/mm^3, hemoglobin (Hgb) greater than or equal to 8 Gm/dL.

Design:

A randomized Phase II study evaluating the role of combining docetaxel with PANVAC[TM]-V
(recombinant vaccinia containing the genes encoding for CEA, MUC-1, lymphocyte
function-associated antigen 3 (LFA-3), intercellular adhesion molecule 1 (ICAM-1) and B7.1)
and PANVAC[TM]-F (recombinant fowlpox containing the genes encoding for CEA, MUC-1, LFA-3,
ICAM-1 and B7.1) vs. docetaxel alone to determine if the addition of the vaccine can prolong
the time to disease progression as well as overall survival in patients with metastatic
breast cancer.

Patients randomized to docetaxel alone may receive sequential therapy with PANVAC[TM]-V and
PANVAC[TM]-F at time of disease progression.

In patients randomized to the concurrent therapy, PANVAC[TM]-V will be administered to
patients 3 weeks prior to the start of chemotherapy as the initial vaccine.

The immune responses to CEA and MUC-1 will then be boosted by administration of
PANVAC[TM]-F.

Sargramostim or granulocyte macrophage colony stimulating factor (GM-CSF) will be
administered with each vaccine inoculation for four consecutive days only for patients
treated at the National cancer Institute (NCI).

Inclusion Criteria


- INCLUSION CRITERIA:

- Metastatic Breast Cancer (either male or female) with evidence of metastatic disease
(must have radiographic evidence of measurable disease) on computed tomography (CT)
scan or X-ray, or evidence of evaluable disease on bone scan that is consistent with
metastasis and a life expectancy of at least 4 months. Patients may have received
unlimited prior hormonal therapy and chemotherapy.

- Histologically confirmed adenocarcinoma of the breast cancer confirmed in the
Pathology Clinical Center at National Cancer Institute (NCI), (or National Naval
Medical Center (NNMC)) or MD Anderson Pathology Department prior to starting this
study. Note: However, if no pathologic specimen is available, patients may enroll
with a clinical course consistent with breast cancer and a pathological documentation
of the disease.

- 18 years of age or greater.

- May have received docetaxel in the adjuvant setting at least 12 months prior to study
entry.

- Able to understand and give informed consent.

- Able to avoid close household contact (close household contacts are those who share
housing or have close physical contact) for at least two weeks after recombinant
vaccinia vaccination with persons with active or a history of 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 3 years of age and under; and immunodeficient or immunosuppressed persons
(by disease or therapy), including human immunodeficiency virus (HIV) infection. We
have vaccinated over 700 cancer patients and have reported no cases of either self
inoculation or person to person transmission of the virus.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.

- Serum creatinine less than 1.5 times upper limits of normal (ULN) OR creatinine
clearance on a 24 hour urine collection of greater than or equal to 60 mL/min,
standard liver function tests (LFT) limitations for patients receiving docetaxel
therapy include bilirubin within ULN and serum glutamic oxaloacetic transaminase
(SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 1.5 times the ULN. If
transaminases are greater than 1.5 times the ULN up to 2 times the ULN (as currently
indicated), then alk phos should be less than 2.5 times the ULN. (Patients with
renal abnormalities should be evaluated for creatinine clearance (CrCl) and
interstitial abnormalities. A Cr Cl of greater than or equal to 60ml/min measured or
calculated and proteinuria less than 1000mg per 24 hours are eligible unless
explained by non-renal causes.)

- Recovered completely from any grade 3 or 4 reversible hematologic and non hematologic
toxicity associated with recent therapy. Typically this is 3-4 weeks for patients who
most recently received cytotoxic therapy. Patients previously treated with mitomycin
c or carboplatin will require a minimum of 6 weeks.

- Hematological eligibility parameters (within 16 days of starting therapy):

1. Granulocyte count greater than or equal to1,500/mm^3

2. Platelet count greater than or equal to 100,000/mm^3

3. Hemoglobin (Hgb) greater than or equal to 8 Gm/dL

- Must agree to use effective birth control or abstinence during and for a period of 4
months after the last vaccination therapy.

- Patients whose tumors are estrogen receptor (ER) positive should have failed primary
hormone therapy unless clinically indicated, i.e. in patients with visceral disease
or symptomatic bone disease where up front chemotherapy is warranted. Patients who
progressed or recurred following Trastuzumab (Herceptin) therapy if a patient is
fluorescence in situ hybridization (FISH) positive or immunohistochemistry (IHC) 3+
positive for human epidermal growth factor receptor 2 (Her-2 neu). Those patients who
have progressed on trastuzumab may continue to receive the drug by their referring
physician. However, if trastuzumab has been discontinued at the time of enrolling on
study, it cannot be resumed while a patient remains on study.

- Patients randomized to docetaxel alone (arm B) may at time of progression go on to
receive vaccine alone if their ECOG performance status remains 0-1, and they do not
have any uncontrolled pain or organ dysfunction that would require another
intervention such as radiation or chemotherapy.

Furthermore, patients initially randomized to arm B that would like to cross over and
continue vaccine therapy must meet on-study eligibility and exclusion criteria with the
exception of liver transaminase requirement. Patients with liver transaminase levels
within Grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (up to 3 x
ULN) will be allowed to crossover to vaccine.

- Patients should appear clinically stable (in the opinion of the principle
investigator) to complete the full 3 month course of vaccination with an anticipated
survival of 6 months or longer.

- No other active malignancies within the past 12 months (with the exception of
non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening
illnesses.

- Patients with cardiovascular symptoms should be fully evaluated for signs and
symptoms of cardiovascular disease and other standard evaluations including
electrocardiogram (EKG), chest X-ray, cardiac enzymes, and echocardiogram as
clinically indicated.

EXCLUSION CRITERIA:

- Patients should have no evidence of being immunocompromised as listed below.

1. Human immunodeficiency virus positivity due to the potential for decreased
tolerance and risk for severe side effects

2. Active autoimmune diseases requiring treatment or a history of autoimmune
disease that might be stimulated by vaccine treatment. This requirement is due
to the potential risks of exacerbating autoimmunity Patients with endocrine
disease that is controlled by replacement therapy including thyroid disease and
adrenal disease and vitiligo may be enrolled

3. Concurrent use of systemic steroids, except for local (topical, nasal, or
inhaled) steroid use

- History of allergy or untoward reaction to prior vaccination with vaccinia virus.

- Pregnant or breast-feeding women

- Altered immune function, including immunodeficiency or history of immunodeficiency;
eczema; history of eczema, or other eczematoid skin disorders; or those with acute,
chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo,
varicella zoster, severe acne, or other open rashes or wounds)

- Serious intercurrent medical illness which would interfere with the ability of the
patient to carry out the treatment program, including, but not limited to,
inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active
diverticulitis

- Clinically active brain metastasis, or a history of seizures that have been active
within one year

- Medical conditions, which, in the opinion of the investigators would jeopardize the
patient or the integrity of the data obtained

- Prior docetaxel chemotherapy for metastatic disease

- Serious hypersensitivity reaction to egg products

- Clinically significant cardiomyopathy requiring treatment

- Chronic hepatitis infection, including B and C, because of potential immune
impairment

- Although topical steroids are allowed, steroid eye-drops are contraindicated

- Patients who have received prior PANVAC vaccine therapy

- Patients with a prior history of allergy to eggs or egg products should not receive
the vaccine

- Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with
ordinary physical activity (New York Heart Association class 2 or greater) are not
eligible.

- Prior splenectomy.

- Cardiac complications, including recent myocardial infarction or cerebrovascular
accident within one year, and/or unstable or uncontrolled angina.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free Survival (PFS)

Outcome Description:

Time between the first day of treatment and disease progression. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progressive disease is a minimum of 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new measurable lesions.

Outcome Time Frame:

19.7 months

Safety Issue:

No

Principal Investigator

James L Gulley, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

050229

NCT ID:

NCT00179309

Start Date:

September 2005

Completion Date:

May 2014

Related Keywords:

  • Breast Cancer
  • CEA
  • MUC-1
  • Immunotherapy
  • GM-CSF
  • Vaccine
  • Breast Cancer
  • Metastatic Breast Cancer
  • Breast Neoplasms

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892
U.T.M.D. Anderson Cancer CenterHouston, Texas  77030