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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Multicenter, Phase II Open-Labeled, Single-Arm Clinical and Pharmacology Study of Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer

Conditions
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Metastatic Breast Cancer, Lung Cancer

Intervention / Treatment
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* Drug: Dichloroacetate (DCA)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dichloroacetate (DCA)<br>Dichloroacetate, 6.25mg/kg orally, twice daily, administered with food around the same time every day and at approximately 8-12 hours apart. | Drug: Dichloroacetate (DCA)<br>* Dichloroacetate, 6.25mg/kg orally, twice daily, administered with food around the same time every day and at approximately 8-12 hours apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate by RECIST Criteria of Oral Dichloroacetate in Patients With Recurrent and/or Metastatic and Pretreated Breast and Non-small Cell Lung Cancer. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | upto 72 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic breast cancer, lung cancer, Previously treated metastatic breast cancer, stage IIIb lung cancer, stage IV lung cancer