Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

DCA starting at an initial dose of 3mg/kg twice daily PO for consecutive days (days 1-5) on a 28 days cycle up to 6 cycles unless evidence of tumour progression. Each dose to be administered with food at the same time everyday 12 hours apart.

Dichloroacetate (DCA)

Bassam Abdulkarim, MD, FRCPC

This is a study to see whether radiotherapy plus chemotherapy (Temozolomide) plus Dichloroacetate (DCA) improves overall survival and offers better control of the disease in patients with newly diagnosed Glioblastoma Multiforme Tumours.

Patients with newly diagnosed Glioblastoma Multiforme Tumours, once consented to the study, would undergo standard treatment of radiotherapy plus chemotherapy (TMZ) with DCA in pill form (twice a day) during the radiation phase of the study and then with TMZ for six months after. Other elements of the clinical trial include pharmacokinetics and MGMT genetic testing.

Combining Radiotherapy and Temozolomide With Dichloroacetate in Patients With Newly Diagnosed Glioblastoma

A Phase I Single Arm Trial Combining Radiotherapy and Temozolomide With Dichloroacetate (DCA) in Patients With Newly Diagnosed Glioblastoma Multiform Tumours

AHS Cancer Control Alberta

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Breast Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

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

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

Edward Garon, MD

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.

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.

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

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

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

Jonsson Comprehensive Cancer Center

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Stage II breast cancer

Stage IV NSCLC

stage at diagnosis

ECOG status 0

ECOG status 1

ECOG status 2

ECOG status

Stage 1 has best prognosis and stage IV has worst.Grade 1 is associated with best prognosis and grade 3 with poor prognosis.ECOG performance status grades a person's overall well-being and scaled from 0-5.ECOG of 0 is associated with best prognosis.Patients with ECOG 0-2 are considered well enough to receive additional treatments for their cancer.

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

Intent to treat analysis was performed. Zero patients achieved complete or partial response in this study.

Response Rate by RECIST Criteria of Oral Dichloroacetate in Patients With Recurrent and/or Metastatic and Pretreated Breast and Non-small Cell Lung Cancer.

Completion of Cycle 1 (28 Days)

Completion of Cycle 2 (56 Days)

Nervous System Diseases

Brain Neoplasms

Recurrent disease with previous surgery, radiation therapy and/or chemotherapy

Newly diagnosed disease with no previous therapy

Oral DCA given twice daily for the 24 week period of the study. Continuation of therapy will be indefinite if efficacious.

Kenneth Petruk, MD co-PI

Evangelos D Michelakis, MD co-PI

Connor Maguire MD, investigator

Linda Webster, NP manager

Malignant gliomas, which include Glioblastoma multiforme (GBM), are the most common and most aggressive types of brain cancer, accounting for approximately 60% of primary brain tumors. These tumors are characterized by diverse molecular abnormalities (within the same tumor), which, along with the difficulties of many standard chemotherapies crossing the blood barrier, contribute to the very poor response to therapy and poor survival.

We recently showed that Dichloroacetate (DCA, an inhibitor of the mitochondrial pyruvate dehydrogenase kinase) was able to depolarize cancer (but not normal) mitochondria and induce apoptosis in cancer but not normal tissues. We believe that altering the metabolism of cancers like glioblastoma (DCA switches metabolism from the cytoplasmic glycolysis to the mitochondrial glucose oxidation) we inhibit the resistance to apoptosis that characterizes cancer. Because metabolism (i.e. glycolysis) is the end result of many and diverse molecular pathways, the effects of DCA might be positive in cancers with diverse molecular backgrounds. DCA is also a very small molecule that readily crosses the blood brain barrier. Therefore we hypothesize that DCA will be an effective and relative non-toxic potential therapy for malignant gliomas.

We are conducting a phase II trial with 2 parallel arms: a) patients with newly diagnosed malignant gliomas and b) patients with recurrent gliomas or gliomas that have failed standard therapy (which includes surgery, radiotherapy and chemotherapy). All patients need to have a histological diagnosis. DCA will be given orally and patients will be followed for a minimum of 6 months. The tumor size will be followed by standard MRI or CT criteria and glucose uptake (a direct effect of DCA on the tumor) will be measured by FDG-PET imaging. Several clinical parameters and quality of life will be followed. Potential toxicity (particularly peripheral neuropathy) will be closely followed and dose-de-escalation protocols are in place in case of toxicity. In addition, escape protocols for the application of standard therapy (when appropriate) are in place in patients with no evidence of response to DCA. In vitro studies will be performed in the tissues obtained at the time of surgery (where appropriate) and correlated prospectively with clinical data.

There is limited ability to accept patients outside of Alberta; this is in part because the visit and testing schedule is intense, requiring residence in Edmonton for at least 6 months.

The Safety and Efficacy of DCA for the Treatment of Brain Cancer

A Phase II Open-labeled, Double-arm Clinical Study of Dichloroacetate (DCA) in Malignant Gliomas and Glioblastome Multiforme (GBM) Patients

Capital Health, Canada

University of Alberta

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combining Radiotherapy and Temozolomide With Dichloroacetate in Patients With Newly Diagnosed Glioblastoma	NCT00703859	Glioblastoma	Dichloroacetate...	18 Years -	AHS Cancer Control Alberta
Combining Radiotherapy and Temozolomide With Dichloroacetate in Patients With Newly Diagnosed Glioblastoma	NCT00703859	Glioblastoma	Dichloroacetate...	18 Years -	AHS Cancer Control Alberta
Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL)	NCT01029925	Metastatic Brea... Lung Cancer	Dichloroacetate...	18 Years -	Jonsson Comprehensive Cancer Center
The Safety and Efficacy of DCA for the Treatment of Brain Cancer	NCT00540176	Malignant Gliom...	Dichloroacetate...	18 Years -	University of Alberta
Combining Radiotherapy and Temozolomide With Dichloroacetate in Patients With Newly Diagnosed Glioblastoma	NCT00703859	Glioblastoma	Dichloroacetate...	18 Years -	AHS Cancer Control Alberta
Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL)	NCT01029925	Metastatic Brea... Lung Cancer	Dichloroacetate...	18 Years -	Jonsson Comprehensive Cancer Center

Spots Global Cancer Trial Database for dichloroacetate (dca)