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

NCT ID: NCT03146962

Last Updated: 2024-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-29
• Study Completion Date: 2023-04-21

Brief 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.

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 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

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).

Conditions

Colorectal Cancer; Pancreatic Cancer; Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: Vitamin C + Surgery

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort B: Vitamin C Only

Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 1

Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 2

Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 3

Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 4

Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 5

A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 6

A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 7

A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Cohort C: Vitamin C + Y-90 Dose Level 8

A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy.

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Interventions

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). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.

Intervention Type: DRUG

Other Intervention Names

Ascorbic Acid

Eligibility Criteria

Inclusion Criteria

• Male or female ≥ 18 years of age.
• Patients with histologically proven early stage or locally advanced colorectal adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection (cohort A).
• 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).
• 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).
• ECOG performance status 0-1.
• Life expectancy of at least 6 months.
• All women of child-bearing potential and all sexually active male patients must agree to use effective contraception.

Exclusion Criteria

• 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).
• 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).
• Patients who have received an investigational drug within 21 days of the first dose of study drug.
• Patients who are pregnant or lactating.
• 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.
• 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).
• Patients who have uncontrolled or severe hyponatremia, hypernatremia, SIADH, hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia
• 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.
• Patients who require therapeutic doses of warfarin
• Patients who have uncontrolled seizure disorder, ascites, iron overload, edema, or dehydration.
• Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, or other conditions predisposing patient to hemolysis.
• Patients who have a known history of recurrent oxalate renal calculi or multiple oxalate.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stand Up To Cancer

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manish Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

New York-Presbyterian Brooklyn Methodist Hospital

Brooklyn, New York, United States

Weill Cornell Medical College

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1610017688

Identifier Type: -

Identifier Source: org_study_id