IV Ascorbic Acid in Advanced Gastric Cancer

Phase Ⅲ Study of IV Ascorbic Acid in Combination With XELOX vs Treatment With XELOX Alone as First-line Therapy for Advanced Gastric Cancer

Linus Pauling and Dr Ewan Cameron have published two retrospective studies about using high dose vitamin C to treat cancer patients forty years ago. Their studies have shown that high dose vitamin C usage could significantly prolong overall survival of patients with advanced cancer. Recently, preclinical study has shown that human colorectal cancer cells harboring KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose of AA impairs tumor growth in Apc/KRASG12D mutant mice. Previous phaseⅠclinical trials have found that high dose (1.5g/kg or 90g/m2) iv AA is well tolerated in cancer patients. This protocol is a phase Ⅲ, study of ascorbic acid (AA) infusions combined with treatment with mFOLOX6 versus mFOLOX6 alone as first-line therapy in patients with recurrent or advanced gastric cancer.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: ascorbic acid; Drug: mFOLFOX6

Detailed Description

Linus Pauling and Dr Ewan Cameron have published two retrospective studies about using high dose vitamin C to treat cancer patients forty years ago. Their studies have shown that high dose vitamin C usage could significantly prolong overall survival of patients with advanced cancer. Recently, preclinical study has shown that human colorectal cancer cells harboring KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose of AA impairs tumor growth in Apc/KRASG12D mutant mice. Previous phaseⅠclinical trials have found that high dose (1.5g/kg or 90g/m2) iv AA is well tolerated in cancer patients. This protocol is a phase Ⅲ, study of ascorbic acid (AA) infusions combined with treatment with mFOLOX6 versus mFOLOX6 alone as first-line therapy in patients with recurrent or advanced gastric cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Medical Oncology,Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age≥18 years, ≤75 years; Histologically proven metastatic adenocarcinoma of stomach (stage 4 disease), unresectable metastatic disease; G6PD status > lower limit of normal; Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2; Life expectancy of at least 12 weeks; ANC ≥1,500/mm3; Hemoglobin > 8g/dL; platelet ≥ 100,000/mm3; Laboratory at baseline evaluation for inclusion in the study: creatinine ≤1.5X upper limit [if the creatinine is elevated, but ≤1.5X the ULN, a 24 hour ;creatinine clearance will be obtained, Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)]; Transaminase (AST/ALT) ≤2.5X upper limit of normal and bilirubin levels ≤1.5X upper limit of normal without liver metastasis; Transaminase (AST/ALT) ≤5X upper limit of normal and bilirubin levels ≤1.5X upper limit of normal with liver metastasis; Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the study; Written informed consent

Exclusion Criteria:

Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 12 months prior to registration on study); Surgery (excluding diagnostic biopsy) or irradiation within 3 weeks prior to study entry; Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment; Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy (palliative radiation therapy allowed) or hormone therapy not indicated in the study protocol; Brain metastasis (known or suspected); Pregnant or lactating women; Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection; Known allergy or any other adverse reaction to any of the drugs or to any related compound; Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin; Patients who are on strong inducers of CYP3A4 which include but are not limited to: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Dexamethasone, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort; Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent; Organ allograft requiring immunosuppressive therapy; Patients with HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ascorbic Acid with mFOLFOX6 group; Ascorbic Acid with mFOLFOX6 Ascorbic Acid (20g/day, D1-3) every 2 weeks mFOLOX6: Oxaliplatin 85 mg/m² d1 concurrent with; Leucovorin 400 mg/m², followed by; Bolus 5FU 400 mg/m² , followed by; Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks	Drug: ascorbic acid; 20g/day, D1-3, every 2 weeks; Other Names: vitamin C; Drug: mFOLFOX6; mFOLFOX6; Oxaliplatin 85 mg/m² d1 concurrent with; Leucovorin 400 mg/m², followed by; Bolus 5FU 400 mg/m² , followed by; Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks; Other Names: chemotherapy
Active Comparator: mFOLFOX6 group; mFOLOX6: Oxaliplatin 85 mg/m² d1 concurrent with; Leucovorin 400 mg/m², followed by; Bolus 5FU 400 mg/m² , followed by; Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks	Drug: mFOLFOX6; mFOLFOX6; Oxaliplatin 85 mg/m² d1 concurrent with; Leucovorin 400 mg/m², followed by; Bolus 5FU 400 mg/m² , followed by; Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks; Other Names: chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Time-to-event outcome measure (initial disease progression) measured in days from cycle 1 day 1 to day of first progression as defined by RECIST1.1 criteria from NCI	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time to event outcome measure (death), measured in days from cycle 1 day 1	up to 5 years
Response Rate	To utilize CT or PET/CT scans to assess overall tumor response rate (complete and partial response) and evaluate disease progression in subjects with advanced or recurrent RAS mutant colorectal cancer treated with the combination of ascorbic acid and FOLOX/FORFIRI +/- bevacizumab versus treatment with FOLFOX/FORFIRI +/- bevacizumab alone	up to 5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Rui-hua Xu, MD.,PhD., Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2017
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: January 8, 2017
• First Submitted That Met QC Criteria: January 8, 2017
• First Posted (Estimate): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): May 18, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: GCV 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No