IV Ascorbic Acid in Advanced Gastric Cancer

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03015675

Collaborator

(none)

200

Enrollment

Location

Arms

32.7

Anticipated Duration (Months)

6.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: ascorbic acid Drug: mFOLFOX6	Phase 3

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 12, 2017

Anticipated Primary Completion Date :

Dec 1, 2017

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression Free Survival [up to 5 years]
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

Secondary Outcome Measures

Overall Survival [up to 5 years]
Time to event outcome measure (death), measured in days from cycle 1 day 1
Response Rate [up to 5 years]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Oncology,Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510060

Sponsors and Collaborators

Sun Yat-sen University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ruihua Xu, Clinical Professor, Sun Yat-sen University

ClinicalTrials.gov Identifier:

NCT03015675

Other Study ID Numbers:

GCV 001

First Posted:

Jan 10, 2017

Last Update Posted:

May 18, 2017

Last Verified:

Mar 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Stomach Neoplasms

Ascorbic Acid

Study Results

No Results Posted as of May 18, 2017