Valproic Acid in Combination With FEC100 for Primary Therapy in Patients With Breast Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/17/2018 |
| Start Date: | December 10, 2008 |
| End Date: | July 29, 2011 |
A Phase II Study of Valproic Acid in Combination With FEC100 for Primary Therapy in Patients With Locally Advanced or Primary Metastatic Breast Cancer
The drugs FEC 100 (5-fluorouracil, epirubicin, and cyclophosphamide) are one of the approved
options to treat Locally Advanced or Primary Metastatic Breast Cancer. In this study, the
investigators will add another drug called Valproic Acid (VPA) to see whether this makes the
treatment better. The addition of Valproic Acid to chemotherapy has been studied in about 65
subjects with cancer and was found to be safe and tolerable. Valproic Acid is approved by the
Food and Drug Administration (FDA) for the treatment of seizures, mood swings, and migraine
headaches. It is not currently approved for cancer, which is why the investigators are
conducting this study.
The results of a Phase I study of Valproic Acid and FEC100 in subjects with cancer that has
spread has led the investigators to believe that this combination is better than just the
standard treatment alone. The investigators are now testing the combination in a study with
subjects who have either a large tumor, many lymph nodes involved or patients whose tumor has
spread. In addition to the treatment, a main goal of the study is to find out which subjects
will benefit from this combination. In the Phase I trial the investigators noticed that while
this combination appears to make the chemotherapy more effective, it did not appear to cause
more side effects induced by the chemotherapy.
options to treat Locally Advanced or Primary Metastatic Breast Cancer. In this study, the
investigators will add another drug called Valproic Acid (VPA) to see whether this makes the
treatment better. The addition of Valproic Acid to chemotherapy has been studied in about 65
subjects with cancer and was found to be safe and tolerable. Valproic Acid is approved by the
Food and Drug Administration (FDA) for the treatment of seizures, mood swings, and migraine
headaches. It is not currently approved for cancer, which is why the investigators are
conducting this study.
The results of a Phase I study of Valproic Acid and FEC100 in subjects with cancer that has
spread has led the investigators to believe that this combination is better than just the
standard treatment alone. The investigators are now testing the combination in a study with
subjects who have either a large tumor, many lymph nodes involved or patients whose tumor has
spread. In addition to the treatment, a main goal of the study is to find out which subjects
will benefit from this combination. In the Phase I trial the investigators noticed that while
this combination appears to make the chemotherapy more effective, it did not appear to cause
more side effects induced by the chemotherapy.
Each year, more than 200,000 patients are diagnosed with breast cancer. While recent advances
in diagnosis and treatment have rendered a large proportion of these patients curable, many
patients still present with either locally advanced or metastatic breast cancer that is not
amenable to potentially curative surgery. To enhance the chance of complete surgical
resection of the tumor, patients with very large, locally advanced or inflammatory breast
cancer will be offered neo-adjuvant therapy.
The use of systemic chemotherapy after the surgical therapy for patients with operable
disease has been associated with a 25%-35% reduction in the risk of systemic relapse (Early
Breast Cancer Trialists' Collaborative Group, 1998) Administration of chemotherapy prior to
surgery, also referred to as neoadjuvant chemotherapy is often used in patients with
inoperable, non-metastatic breast cancer. However more recently, neoadjuvant therapy has
become more commonly used as it allows the direct assessment of response to systemic therapy
and the collection of biological markers of therapy that are otherwise difficult to obtain.
Furthermore, the relative high response rate allows the ability to surgically remove the
tumor and achieve adequate tumor-free margins.
in diagnosis and treatment have rendered a large proportion of these patients curable, many
patients still present with either locally advanced or metastatic breast cancer that is not
amenable to potentially curative surgery. To enhance the chance of complete surgical
resection of the tumor, patients with very large, locally advanced or inflammatory breast
cancer will be offered neo-adjuvant therapy.
The use of systemic chemotherapy after the surgical therapy for patients with operable
disease has been associated with a 25%-35% reduction in the risk of systemic relapse (Early
Breast Cancer Trialists' Collaborative Group, 1998) Administration of chemotherapy prior to
surgery, also referred to as neoadjuvant chemotherapy is often used in patients with
inoperable, non-metastatic breast cancer. However more recently, neoadjuvant therapy has
become more commonly used as it allows the direct assessment of response to systemic therapy
and the collection of biological markers of therapy that are otherwise difficult to obtain.
Furthermore, the relative high response rate allows the ability to surgically remove the
tumor and achieve adequate tumor-free margins.
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed diagnosis of breast
cancer
- Patients must have "locally advanced" adenocarcinoma of the breast:
- tumors > 2 cm without lymph node involvement (negative sentinel lymph node
mapping)
- tumors > 2 cm with lymph node involvement (either by positive sentinel lymph node
mapping or FNA of palpable lymph node)
- tumors of any size that show extension to the chest wall or skin, including
edema, ulceration, or satellite skin nodules
- inflammatory carcinoma (stage IIIB) that is amenable to surgery
- tumors of any size associated with ipsilateral internal mammary nodes (stage
IIIB)
- tumors of any size associated with ipsilateral supraclavicular lymph nodes (IIIC)
without other evidence of systemic metastases
- patients may have bilateral breast cancer if both breasts are assessible for
response
- Age >18 years
- Because no dosing or adverse event data are currently available on the use of VPA in
combination with FEC100 in patients <18 years of age, children are excluded from this
study
- ECOG performance status 0 or 1 (Karnofsky >80%)
- Patients must have normal organ and marrow function as defined below:
- leukocytes >3,000/mcL
- absolute neutrophil count >1,500/mcL
- platelets >100,000/mcL
- total bilirubin within 1.5 x normal institutional limits
- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits
- VPA has been associated with neural tube defects in the developing human fetus, for
this reason and because FEC100 used in this trial are also known to be teratogenic,
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation. Participating men must use condoms while on study
and for at least 3 months after the trial has ended. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Patients may not have had any prior chemotherapy within the last 2 years
- Patients may not have been exposed to prior anthracyclines
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases are excluded
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to VPA or FEC100.
- Patients with known congestive heart disease or LVEF fractions of <50 % (past or
current), patients with known ventricular arrhythmias
- Patients taking VPA as an anti-seizure agent or for any other indications
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Due to the teratogenic effects of VPA and FEC100, pregnant or lactating women are
excluded from the study.
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