Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL)

In the United States, approximately 180,000 new cases of breast cancer occur annually, and
there are more than 40,000 deaths. More than 150,000 cases develop each year in Canada and
the European community together, resulting in over 60,000 deaths from breast cancer. The
vast majority of patients who die from breast cancer succumb to metastatic disease.
Endocrine therapy and chemotherapy (using either sequential single agents or combination
regimens) remain the principal treatments for women with metastatic breast cancer. A wide
variety of classes of chemotherapeutic agents have activity as single agents. Median
survival remains approximately two years for women with metastatic breast cancer, and less
than 3% of patients will experience long-term survival after treatment. The development of
new treatment strategies is therefore essential to improve outcome for patients with
metastatic breast cancer. The population selected for this study will have previously
received, where appropriate, those drugs with clearly defined survival advantages
(anthracyclines, taxanes, trastuzumab, and hormonal therapy).

Patients with metastatic non-small cell lung cancer are considered incurable. Palliative
chemotherapies, such as platinum-based doublet, Taxotere or Pemetrexed or Erlotinib (an
epidermal growth factor tyrosine kinase) have been proven to improve symptoms, and survival
in patients with good performance status. Despite these treatments, the median survival of
metastatic non-small cell lung cancer is about one year. Therefore, there is an urgent need
to develop novel therapy in these patients.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed metastatic breast cancer
or Stage IIIb or IV non-small cell lung cancer.

- Must have measurable disease as defined by at least one target lesion by RECIST
criteria that has not been irradiated.

- Progressive disease after prior chemotherapy or patient refusal of these chemotherapy
options.

- Breast Cancer

- Patients should have received two prior lines of chemotherapy. This should
include prior anthracycline and taxane therapy, either in the adjuvant or
metastatic setting.

- HER-2 positive breast cancer should have received Trastuzumab, in either
the adjuvant or metastatic setting.

- Estrogen Receptor positive breast cancer should have received at least one
prior hormonal therapy, either in the adjuvant or metastatic setting.

- Non-small cell lung cancer patients should have received at least platinum based
chemotherapy in the adjuvant, neoadjuvant or metastatic setting.

- Age > 18 years.

- ECOG performance status < 2.

- Life expectancy of greater than 12 weeks.

- Patients must have normal organ and marrow function as defined below:

- Absolute neutrophil count >1,500/mcL

- Hemoglobin >9.0 g/dL

- Platelets >100,000/mcL

- Total bilirubin <1.5 X upper limit of normal (ULN)

- AST (SGOT) and ALT (SGPT) <2.5 X ULN or <5 X ULN in the presence of live
metastases.

- Creatinine <1.5 X ULN

- Recovery to baseline or, at most, grade 1 of all drug-related toxicities due to prior
chemotherapy, radiation, hormonal therapy, or molecular targeted therapy, except for
alopecia.

- Ejection fraction by MUGA scan or echocardiogram must be within normal range.

- Women of childbearing potential must have a negative pregnancy test and women and men
must agree to use adequate contraception prior to study entry, for the duration of
study participation and for 30 days after the last dose of study therapy.

- Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

- Patients who have had chemotherapy, hormonal therapy, molecular targeted therapy, or
radiotherapy within 4 weeks prior to receiving first dose of DCA. An exception will
be made for palliative radiation to bone which must have been completed 10 days prior
to the first dose of DCA. An exception will also be made for HER-2 positive BC who
can continue to receive Trastuzumab during therapy with DCA.

- Patients who have not recovered from adverse events due to agents administered more
than 4 weeks earlier.

- Patients may not be receiving any other investigational agents, chemotherapy,
immunotherapy, radiotherapy, or molecular targeted agents.

- Active CNS metastasis.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to DCA.

- Due to the possibility of peripheral sensorimotor neuropathy from DCA, the presence
of any grad peripheral neuropathy due to prior medical condition (such as multiple
sclerosis), medications, or other etiologies.

- Any psychological, familial, sociological, or geographical conditions that do not
permit medical follow-up and compliance with the study protocol.

- Uncontrolled concurrent illness including, but not limited to, ongoing or active
infection (requiring parenteral anti-biotics), symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.

- Pregnant women are excluded from this study.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with DCA.

- 2 years must have elapsed since the initial curative procedure for other
malignancies, except for in situ cervical cancer, non-melanoma skin cancer, and
localized prostate cancer after curative therapy such as surgery, or radiation.

- Patient history of inflammatory bowel disease, malabsorption syndrome, condition
causing chronic diarrhea and requiring active therapy or substantial amount of small
bowels or stomach removed that may impair absorption of DCA.

- Therapeutic anticoagulation will be allowed with Heparin or LMWH but not with
Coumadin.

- Any history of nephrolithiasis because of possible increase in urinary oxalate with
DCA and correlation with nephrolithiasis.