Study of DCA (Dichloroacetate) in Combination With Cisplatin and Definitive Radiation in Head and Neck Carcinoma

NCT01386632 | Completed Phase 2 Results DMC

• 1 other identifier: DCA 2010
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

This will be a randomized masked placebo-controlled single-center study to evaluate the effects of Dichloroacetate (DCA) versus placebo given in combination with Cisplatin and radiation treatment in patients with Stage III-IV Squamous Cell Carcinoma of the Head and Neck (SCCHN). Fifty subjects will be enrolled and randomly assigned on a 1:1 ratio to DCA or matching placebo given with standard of care treatment consisting of Cisplatin and radiation treatment. Patients will receive DCA/placebo PO or per G-tube twice a day for 8 weeks. The first 6 patients of the total study population will represent a safety lead-in cohort. The results of the safety lead-in of DCA/placebo in combination with Cisplatin and radiation therapy will be evaluated after the 6th patient has completed 8 weeks of therapy. Recruitment of patients will be withheld during safety data analysis.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Stage III-IV Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Experienced Adverse Events During Treatment.

  Percentage of Participants Who Experienced Adverse Events During Treatment including but are not limited to mucositis, leucopenia, neuropathy, and treatment breaks. This will be done according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

  Adverse events (AE) will be assessed from the time the subject begins the study until the 30-days after receiving the last dose of the study medication.

Secondary Outcomes (17)

• Two-year Progression-free Survival Rate in Locally Advanced Head and Neck Squamous Cell Carcinoma in Patients Receiving Concurrent Cisplatin, Radiation Therapy, and DCA.

  Year 2

• Two-year and Five-year Progression-free Survival Rate in Locally Advanced Head and Neck Squamous Cell Carcinoma in Patients Receiving Concurrent Cisplatin, Radiation Therapy, and DCA.

  Year 5

• Local Response Rate for Locally Advanced Head and Neck Squamous Cell Carcinoma Patients Receiving Concurrent Cisplatin, Radiation Therapy, and DCA.

  3 months

• Local Response Rate for Locally Advanced Head and Neck Squamous Cell Carcinoma Patients Receiving Concurrent Cisplatin, Radiation Therapy, and DCA.

  1 year

• Overall Survival for Locally Advanced Head and Neck Squamous Cell Carcinoma Patients Receiving Concurrent Cisplatin, Radiation Therapy, and DCA.

  1 year

Study Arms (2)

DCA (dichloroacetate) Treatment

ACTIVE COMPARATOR

DCA orally 12.5mg/kg or per G-tube BID daily for 8 weeks in conjunction with Cisplatin 100 mg/m\^2 IV over 30-60 minutes every 3wks X 3(Days 1, 22, and 43 of RT)and RT 70 Gy/35 -200 cGy/d x 7 weeks (35 Fractions)

Drug: DCA (dichloroacetate)

Placebo

PLACEBO COMPARATOR

Placebo orally or per G-tube BID for 8 weeks in conjunction with Cisplatin 100 mg/m\^2 IV over 30-60 minutes every 3wks X 3(Days 1, 22, and 43 of RT)and RT 70 Gy/35 -200 cGy/d x 7 weeks (35 Fractions)

Drug: Placebo

Interventions

DCA (dichloroacetate) DRUG

DCA orally 12.5mg/kg PO or per G-tube BID daily for 8 weeks in conjunction with Cisplatin 100 mg/m\^2 IV over 30-60minutes every 3wks X 3(Days 1, 22, and 43 of RT)and RT 70 Gy/35 -200 cGy/d x 7 weeks (35 Fractions)

Also known as: dichloroacetate

DCA (dichloroacetate) Treatment

Placebo DRUG

Placebo PO or per G-tube twice a day for 8 weeks given in combination with Cisplatin.

Placebo

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, cytologically confirmed and previously untreated stage 3 or 4 HNSC that recommended treatment would be concurrent cisplatin and radiation.
• Age ≥ 18 years
• ECOG performance status ≤ 2 or Karnofsky ≥70%
• 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 ≥90 g/L
• 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 liver metastases
• Creatinine ≤1.5 X institutional upper limit of normal
• The effects of DCA on the developing human fetus are unknown. For this reason and because DCA can be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (e.g.: hormonal or barrier method of birth control, abstinence)prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand the purpose of the study and the willingness to sign a written informed consent document.
• Repeat biopsy is not mandatory, but is strongly suggested. Should be performed between Day 8 and Day 15 treatments.

You may not qualify if:

• Patients may not be receiving any other investigational agents, chemotherapy, immunotherapy, radiotherapy, or molecular targeted agents.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that could confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to DCA.(Cetuximab)
• Due to the possibility of peripheral sensorimotor neuropathy from DCA, the presence of grade 2 or higher peripheral neuropathy due to a 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 intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements. Specifically, for patients who are taking either or both oral hypoglycemics and insulin for diabetes mellitus will not be eligible as DCA in combination with these agents may increase the risk of clinically significant hypoglycemia, compromising patient safety.
• Pregnant or breast-feeding women are excluded from this study because DCA is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DCA, breastfeeding should be discontinued if the mother is treated with DCA.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with DCA. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Five years must have elapsed since the initial curative procedure for other malignancies, except for in situ cervical cancer, basal cell carcinoma of the skin, and localized prostate cancer after curative therapy such as surgery, or radiation.
• History of malabsorption syndrome or substantial amount of small bowels or stomach removed that may impair absorption of DCA.

Sponsors & Collaborators

• Sanford Health: lead

Study Sites (2)

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

Sanford Hematology and Oncology

Sioux Falls, South Dakota, 57104, United States

Location

Related Publications (1)

• Powell SF, Mazurczak M, Dib EG, Bleeker JS, Geeraerts LH, Tinguely M, Lohr MM, McGraw SC, Jensen AW, Ellison CA, Black LJ, Puumala SE, Reed VJ, Miskimins WK, Lee JH, Spanos WC. Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma. Invest New Drugs. 2022 Jun;40(3):622-633. doi: 10.1007/s10637-022-01235-5. Epub 2022 Mar 21.

  PMID: 35312941 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Dichloroacetic Acid

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Steven Powell
• Organization: Sanford Clinical Research

patientquestionsSHDCA@sanfordhealth.org

605-328-8000

Study Officials

• Steven F Powell, MD

  Sanford Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2011
• First Posted: July 1, 2011
• Study Start: May 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: June 1, 2020
• Last Updated: October 27, 2020
• Results First Posted: June 14, 2017

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)