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

• Status: Recruiting
• Trial end date: 2023-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Weill Medical College of Cornell University
• Collaborator: Stand Up To Cancer
• Treatments: Ascorbic Acid; Vitamins

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.