Clinical Trials /

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

NCT03146962

Description:

This is a multicenter, single arm, 3-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 extended RAS (e.g.KRAS or NRAS) or BRAF mutation metastatic cancer who have received prior systemic treatment (cohort B). Cohort C will involve patients with colorectal cancer having an extended RAS or BRAF mutation who are amenable for localregional therapy of hepatic metastases with Yttrium-90 radioembolization.

Related Conditions:
  • Colorectal Adenocarcinoma
  • Lung Carcinoma
  • Malignant Solid Tumor
  • 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 multicenter, single arm, 3-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 extended RAS (e.g.KRAS or NRAS) or BRAF mutation metastatic cancer who have received prior systemic treatment (cohort B). Cohort C will involve patients with colorectal cancer having an extended RAS or BRAF mutation who are amenable for localregional therapy of hepatic metastases with Yttrium-90 radioembolization.

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).
      For Cohort C, the primary objective is to determine that maximal tolerated dose of the
      combination of high dose vitamin C with Y90 radioembolization for patients solid tumor
      malignancies and liver metastases amenable to local-regional therapy

      Patients in cohort A receive a high dose vitamin C infusion for 4 days per week for 2-4
      consecutive weeks prior to surgery. Patients in cohort B receive high dose vitamin C infusion
      for 4 days per week for up to 6 months or disease progression. Cohort C will receive high
      dose vitamin C for 1-2 weeks prior to and following Y90 radioembolization of hepatic
      metastases

      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)

        -  Patients with metastatic cancer with an extended RAS (e.g. KRAS or NRAS) or BRAF
           mutation with liver metastases amenable to Y90 radioembolization (cohort C).
    

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). Cohort C will receive high dose vitamin C for 1-2 weeks prior to and following Y90 radioembolization of hepatic metastases
  • 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
             (cohort A).

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

             Note: If subject refuses chemotherapy and therefore has no prior chemotherapy, they
             can be eligible for the trial with approval from the primary investigator.

             3.1 Patients with metastatic cancer with an extended RAS (e.g. KRAS or NRAS) or BRAF
             mutation with liver metastases amenable to Y90 radioembolization (cohort C).

          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 ≥ 1000 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).

          9. Patients taking Vitamin C will have stopped taking oral vitamin C more than 1 week
             before planned study treatment.

         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).

        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. a. Most of the
        known interactions with vitamin C are from oral use and acidification of the stomach
        lining. There are few known interactions with high dose intravenous vitamin C. We recommend
        not using deferoxamine as there may be an association with ventricular dysfunction (unknown
        mechanism).

        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 require therapeutic doses of warfarin is prohibited.

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

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

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

Primary Outcome Measures

Measure:Change in antitumor activity measured by pathologic response based on tumor regression grading in cohort A patients.
Time Frame:cohort A - 8 weeks
Safety Issue:
Description:measured by tissue analysis of tumor cell death and fibrotic response in Cohort A subjects

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:cohort B - up to 6 months cohort C - 16 weeks
Safety Issue:
Description:Defined as the time from registration to cancer progression or death due to any cause
Measure:Objective response rate (ORR)
Time Frame:cohort B - up to 6 months cohort C - 16 weeks
Safety Issue:
Description:Examination of patients with a partial response or complete response based on RECIST 1.1 Criteria.
Measure:Assessment of pharmacokinetics of high dose vitamin C plasma levels concentrations
Time Frame:cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks
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, Cohort C - 16 weeks
Safety Issue:
Description:

Details

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

Last Updated

February 27, 2020