Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL)
Condition: Metastatic Breast Cancer; Lung Cancer
MeSH terms: Breast Neoplasms; Lung Neoplasms
Intervention: Dichloroacetate (DCA)
Intervention description: Dichloroacetate, 6.25mg/kg orally, twice daily, administered with food around the same time every day and at approximately 8-12 hours apart
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic breast cancer; lung cancer; Previously treated metastatic breast cancer; stage IIIb lung cancer; stage IV lung cancer

Summary:

      The purpose of this study is to determine the response rate by RECIST criteria of oral
      dichloroacetate in patients with recurrent and/or metastatic and pretreated breast and
      non-small cell lung cancer.
    

Eligibility criteria:

        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.