Clinical Trials /

High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies

NCT03146962

Description:

This is a single arm, 2-cohort, open-label trial of high dose Vitamin C intravenous infusion in subjects with solid tumor malignancies who are eligible for resection (cohort A) or with KRAS or BRAF mutant metastatic cancer who have received prior systemic treatment (cohort B).

Related Conditions:
  • Colorectal Adenocarcinoma
  • Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies
  • Official Title: A Phase II Study of High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 1610017688
  • NCT ID: NCT03146962

Conditions

  • Colorectal Cancer
  • Pancreatic Cancer
  • Lung Cancer

Interventions

DrugSynonymsArms
Vitamin CAscorbic AcidAll Subjects

Purpose

This is a single arm, 2-cohort, open-label trial of high dose Vitamin C intravenous infusion in subjects with solid tumor malignancies who are eligible for resection (cohort A) or with KRAS or BRAF mutant metastatic cancer who have received prior systemic treatment (cohort B).

Detailed Description

      This clinical trial is for men and women with resectable or metastatic solid tumor
      malignancies. The objective of the study is to investigate whether high dose vitamin C
      infusion leads to pathological tumor response in resectable colorectal, pancreatic, and lung
      cancer (cohort A) or objective tumor response in KRAS or BRAF mutant solid tumors (cohort B).

      Patients enrolled in cohort A will receive high dose Vitamin C infusion for 4 days per week
      for 2-4 consecutive weeks prior to surgery. Patients enrolled in cohort B will receive high
      dose Vitamin C infusion for 4 days per week up to 6 months. A tumor sample will be resected
      after completion of study drug (high dose vitamin C infusion) treatment to examine the
      effects of study drug (Cohort A only). In addition, organoids will be grown in vitro and
      continue to be treated with vitamin C added in culture medium to examine tumor response. The
      resected tumor in this study will

      Key eligibility:

        -  Men and women age 18 and older

        -  Patients with histologically proven early stage or locally advanced colorectal
           adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection, and
           have not received chemotherapy or radiotherapy (cohort A) Patients with inoperable,
           metastatic, KRAS or BRAF mutant colorectal adenocarcinoma, lung cancer and pancreatic
           cancer, who have received at least 1 line of treatment for metastatic disease (cohort B)
    

Trial Arms

NameTypeDescriptionInterventions
All SubjectsExperimentalVitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B).
  • Vitamin C

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female ≥ 18 years of age.

          2. Patients with histologically proven early stage or locally advanced colorectal
             adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection, and
             have not received chemotherapy or radiotherapy (cohort A)

          3. Patients with inoperable, metastatic, KRAS or BRAF mutant colorectal adenocarcinoma,
             lung cancer and pancreatic cancer, who have received at least 1 line of treatment for
             metastatic disease (cohort B).

          4. ECOG performance status 0-1.

          5. Life expectancy of at least 6 months.

          6. All women of child-bearing potential and all sexually active male patients must agree
             to use effective contraception.

          7. Patient with adequate organ and marrow function as follows:

               -  ANC ≥ 1500 mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL,

               -  serum creatinine ≤1.8 mg/dL or creatinine clearance > 50 mL/min (Appendix C:
                  Estimating Creatinine Clearance);

               -  bilirubin ≤ 1.5 mg/dL; alanine aminotransferase (ALT), aspartate transaminase
                  (AST) ≤ 2.5 times the upper limit of normal if no liver involvement or ≤ 5 times
                  the upper limit of normal with liver involvement.

          8. Patients with serum electrolytes (including calcium, magnesium, phosphorous, sodium
             and potassium) within normal limits (supplementation to maintain normal electrolytes
             is allowed).

        10. Patients capable of understanding and complying with the protocol and who have signed
        the informed consent document.

        Exclusion Criteria:

          1. Patients with uncontrolled intercurrent illness including, but not limited to
             uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV),
             uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements (Appendix B: New York Heart Association
             (NYHA) Classifications).

          2. Patients with active heart disease including myocardial infarction within previous 3
             months, symptomatic coronary artery disease, arrhythmias not controlled by medication,
             unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and
             IV) (Appendix B: New York Heart Association (NYHA) Classifications).

          3. Patients who have received systemic chemotherapy or targeted therapy for metastatic
             disease within 2 weeks from start of study drug treatment (cohort B).

          4. Patients who have received an investigational drug within 21 days of the first dose of
             study drug.

          5. Patient who have not recovered to grade ≤ 1 from adverse events (AEs) due to
             investigational drugs or other medications, which were administered more than 4 weeks
             prior to the first dose of study drug.

          6. Patients who are pregnant or lactating.

          7. Patients who are known to be positive for the human immunodeficiency virus (HIV). The
             effect of Vitamin C on HIV medications is unknown. Note: HIV testing is not required
             for eligibility, but if performed previously and was positive, the patient is
             ineligible for the study.

          8. Patients who have the inability or unwillingness to abide by the study protocol or
             cooperate fully with the investigator or designee.

          9. Patient who are receiving drugs which are known to interact with Vitamin C, potential
             risk and eligibility will be evaluated individually by the investigator.

         10. Patients who have uncontrolled or severe hyponatremia, hypernatremia, SIADH,
             hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia

         11. Patients who have uncontrolled or severe coagulopathies or a history of clinically
             significant bleeding within the past 6 months, such as hemoptysis, epistaxis,
             hematochezia, hematuria, or gastrointestinal bleeding.

         12. Patients who have a known predisposition for bleeding such as von Willebrand's disease
             or other such condition.

         13. Patients who require therapeutic doses of any anticoagulant, including low molecular
             weight heparin (LMWH). Concomitant use of warfarin, even at prophylactic doses, is
             prohibited.

         14. Patients who have uncontrolled seizure disorder, ascites, iron overload, edema, or
             dehydration.

         15. Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary
             spherocytosis, or other conditions predisposing patient to hemolysis.

         16. Patients who have a history of oxalate renal calculi.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Preliminary antitumor activity measured by pathologic response based on tumor regression grading in cohort A patients. 3-month disease control rate (DCR) will be evaluated using RECIST v 1.1 in cohort B patients.
Time Frame:cohort A - 8 weeks, cohort B - up to 6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival (PFS) in cohort B.
Time Frame:cohort A - 8 weeks, cohort B - up to 6 months
Safety Issue:
Description:
Measure:Objective response rate (ORR) in cohort B.
Time Frame:cohort A - 8 weeks, cohort B - up to 6 months
Safety Issue:
Description:
Measure:Assessment of pharmacokinetics of high dose vitamin C plasma levels concentrations
Time Frame:cohort A - 8 weeks, cohort B - up to 6 months
Safety Issue:
Description:
Measure:Safety of high dose vitamin C administration using CTCAE 4.03.
Time Frame:cohort A - 8 weeks, cohort B - up to 6 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

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