Study of DCA (Dichloroacetate) in Combination With Cisplatin and Definitive Radiation in Head and Neck Carcinoma
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: DCA (dichloroacetate); Placebo
Intervention description: 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); Placebo PO or per G-tube twice a day for 8 weeks given in combination with Cisplatin.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage III-IV Squamous Cell Carcinoma

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.