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Metastatic Breast CancerPhase 2NCT01029925

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

A Phase 2 study testing Dichloroacetate (DCA) in people with Metastatic Breast Cancer and Lung Cancer, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer, Lung Cancer
What is being tested?
Dichloroacetate (DCA)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
Dec 2009to Nov 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of California, Los Angeles

    Los Angeles, California, 90095

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Dichloroacetate (DCA)
Keywords
metastatic breast cancer, lung cancer, Previously treated metastatic breast cancer, stage IIIb lung cancer, stage IV lung cancer
Medical subject headings
Breast Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dichloroacetate (DCA)Drug

    Dichloroacetate, 6.25mg/kg orally, twice daily, administered with food around the same time every day and at approximately 8-12 hours apart

Study groups in NCT01029925
Study groupRoleWhat they receive
Dichloroacetate (DCA)ExperimentalDichloroacetate, 6.25mg/kg orally, twice daily, administered with food around the same time every day and at approximately 8-12 hours apart.
Receives: Drug: Dichloroacetate (DCA)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: upto 72 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2009 (estimated)
  2. Study startDec 2009
  3. Primary completionAug 2011
  4. Study completionNov 2011

Why it stopped: DSMB determined, due to higher than expected risk/safety concerns, study should be closed.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01029925
Sponsor's protocol ID
DCA Breast NSCLC
Other IDs
09-07-013
Status last verified
Jun 2013
First submitted
9 Dec 2009
Last updated
12 Feb 2016
Data monitoring committee
Yes

Publications

  • Kjaer A. Molecular imaging of cancer using PET and SPECT. Adv Exp Med Biol. 2006;587:277-84.

    PubMed 17163171
  • Warburg O. Ueber den stoffweschsel der tumoren (London: Constable). (1930).

  • Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004 Nov;4(11):891-9. doi: 10.1038/nrc1478.

    PubMed 15516961
  • Merida I, Avila-Flores A. Tumor metabolism: new opportunities for cancer therapy. Clin Transl Oncol. 2006 Oct;8(10):711-6. doi: 10.1007/s12094-006-0117-6.

    PubMed 17074669
  • Andersson B, Janson V, Behnam-Motlagh P, Henriksson R, Grankvist K. Induction of apoptosis by intracellular potassium ion depletion: using the fluorescent dye PBFI in a 96-well plate method in cultured lung cancer cells. Toxicol In Vitro. 2006 Sep;20(6):986-94. doi: 10.1016/j.tiv.2005.12.013. Epub 2006 Feb 17.

    PubMed 16483738
  • Remillard CV, Yuan JX. Activation of K+ channels: an essential pathway in programmed cell death. Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L49-67. doi: 10.1152/ajplung.00041.2003.

    PubMed 14656699
  • Wang H, Zhang Y, Cao L, Han H, Wang J, Yang B, Nattel S, Wang Z. HERG K+ channel, a regulator of tumor cell apoptosis and proliferation. Cancer Res. 2002 Sep 1;62(17):4843-8.

    PubMed 12208728
  • Yu SP, Yeh CH, Sensi SL, Gwag BJ, Canzoniero LM, Farhangrazi ZS, Ying HS, Tian M, Dugan LL, Choi DW. Mediation of neuronal apoptosis by enhancement of outward potassium current. Science. 1997 Oct 3;278(5335):114-7. doi: 10.1126/science.278.5335.114.

    PubMed 9311914
  • Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007 Jan;11(1):37-51. doi: 10.1016/j.ccr.2006.10.020.

    PubMed 17222789
  • Garon EB, Christofk HR, Hosmer W, Britten CD, Bahng A, Crabtree MJ, Hong CS, Kamranpour N, Pitts S, Kabbinavar F, Patel C, von Euw E, Black A, Michelakis ED, Dubinett SM, Slamon DJ. Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer. J Cancer Res Clin Oncol. 2014 Mar;140(3):443-52. doi: 10.1007/s00432-014-1583-9. Epub 2014 Jan 18.

    PubMed 24442098

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dichloroacetate (DCA) in people with Metastatic Breast Cancer and Lung Cancer, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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: upto 72 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01029925, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2016.

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