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

NCT01029925 | Terminated Phase 2 Results DMC

• 2 other identifiers: DCA Breast NSCLC09-07-013
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Breast Cancer; Lung Cancer

Keywords

metastatic breast cancer; lung cancer; Previously treated metastatic breast cancer; stage IIIb lung cancer; stage IV lung cancer

Outcome Measures

Primary Outcomes (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

  upto 72 days

Study Arms (1)

Dichloroacetate (DCA)

EXPERIMENTAL

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)

Interventions

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

Dichloroacetate (DCA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Related Publications (10)

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  PMID: 12208728 BACKGROUND

• 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.

  PMID: 9311914 BACKGROUND

• 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.

  PMID: 17222789 BACKGROUND

• 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.

  PMID: 24442098 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms

Interventions

Dichloroacetic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroacetates; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrocarbons

Limitations and Caveats

The greatest limitation in our study was early termination due to perceived lack of drug efficacy leading to small number of subjects analyzed.

Results Point of Contact

• Title: Edward Garon, MD
• Organization: University of California Los Angeles Jonsson Comprehensive Cancer Center

egaron@mednet.ucla.edu

310 586 2098

Study Officials

• Edward Garon, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2009
• First Posted: December 10, 2009
• Study Start: December 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: November 1, 2011
• Last Updated: February 12, 2016
• Results First Posted: February 12, 2016

Record last verified: 2013-06

Locations

US (1)