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

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ClinicalTrials.gov Identifier: NCT03146962
Recruitment Status : Recruiting
First Posted : May 10, 2017
Last Update Posted : July 29, 2019
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Tracking Information
First Submitted Date  ICMJE April 27, 2017
First Posted Date  ICMJE May 10, 2017
Last Update Posted Date July 29, 2019
Actual Study Start Date  ICMJE March 29, 2017
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2017)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03146962 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2017)
  • Progression-free survival (PFS) in cohort B. [ Time Frame: cohort A - 8 weeks, cohort B - up to 6 months ]
  • Objective response rate (ORR) in cohort B. [ Time Frame: cohort A - 8 weeks, cohort B - up to 6 months ]
  • Assessment of pharmacokinetics of high dose vitamin C plasma levels concentrations [ Time Frame: cohort A - 8 weeks, cohort B - up to 6 months ]
  • Safety of high dose vitamin C administration using CTCAE 4.03. [ Time Frame: cohort A - 8 weeks, cohort B - up to 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 9, 2017)
  • In vitro activity of vitamin C in tumor organoids from cohort A patients [ Time Frame: cohort A - 8 weeks, cohort B - up to 6 months ]
    Molecular signature of vitamin C efficacy will be determined using RNA sequencing and compared between KRAS or BRAF mutant vs wild type tumors. Organoids will be prepared from resected tumor samples and treated with vitamin C.
  • Exploratory biomarker samples from tumor tissue will be collected at the time points specified in the protocol. [ Time Frame: cohort A - 8 weeks, cohort B - up to 6 months ]
    To explore potential correlation of gene expression pattern with anti-tumor activity of vitamin C, we plan to perform RNA sequencing using surgical sample in cohort A patients who will receive vitamin C infusion pre-operatively.
  • Pharmacodynamic samples from tumor tissue will be collected at the time points specified in the protocol. [ Time Frame: cohort A - 8 weeks, cohort B - up to 6 months ]
    Immunohistochemical (IHC) staining for GLUT1 protein expression will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues. Immunohistochemical (IHC) staining for phosphor-AMPK will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues to assess AMPK activation.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies
Official Title  ICMJE A Phase II Study of High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies
Brief Summary 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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Pancreatic Cancer
  • Lung Cancer
Intervention  ICMJE Drug: Vitamin C
Vitamin 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).
Other Name: Ascorbic Acid
Study Arms  ICMJE Experimental: All Subjects
Vitamin 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).
Intervention: Drug: Vitamin C
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 9, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alice Mercado, RN 646-962-3080 alm2051@med.cornell.edu
Contact: Scott Sherrin, RN 646-962-3378 sts2039@med.cornell.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03146962
Other Study ID Numbers  ICMJE 1610017688
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Manish Shah, MD Weill Cornell Medicine
PRS Account Weill Medical College of Cornell University
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP