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

This study has been terminated.
(The DSMB determined that due to higher than expected risk and safety concerns the study should be closed.)
Sponsor:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01029925
First received: December 9, 2009
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Lung Cancer
Drug: Herceptin plus DCA
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To further evaluate the safety and tolerability of oral dichloroacetate in patients with recurrent and/or metastatic and pretreated breast and non-small cell lung cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To evaluate the progression-free survival and overall survival achieved with oral dichloroacetate in patients with recurrent and/or metastatic and pretreated breast and non-small cell lung cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the effect of oral dichloroacetate on biomarkers for cell proliferation, mitotic index, and apoptosis in patients with metastatic and pretreated breast and non-small cell lung cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the effect of gluthathione-S-transferase zeta polymorphism on the metabolism and toxicity of oral dichloroacetate in patients with recurrent and/or metastatic and pretreated breast and non-small cell lung cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: December 2009
Study Completion Date: November 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Herceptin plus DCA Drug: Herceptin plus DCA

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01029925

Locations
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Edward Garon, MD University of California, Los Angeles
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01029925     History of Changes
Other Study ID Numbers: DCA Breast NSCLC, 09-07-013
Study First Received: December 9, 2009
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
metastatic breast cancer
lung cancer
Previously treated metastatic breast cancer
stage IIIb lung cancer
stage IV lung cancer

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014