Safety and Efficacy Study of Gemcitabine Combined With High Dose Intravenous Vitamin C (HDIVC) for Patients With Metastatic Adenocarcinoma of the Pancreas

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Eastern Regional Medical Center
ClinicalTrials.gov Identifier:
NCT01654861
First received: July 13, 2012
Last updated: June 26, 2014
Last verified: June 2014
  Purpose
  • The combination of gemcitabine and HDIVC is safe and may favorably change the clinical course for an individual patient.
  • The combination of gemcitabine and HDIVC is synergistic in anti-tumor effect as seen in preclinical models, where HDIVC creates a pro-oxidative effect that adds to the anti-tumor effect of gemcitabine.
  • The combination of gemcitabine and HDIVC may improve Progression Free Survival (PFS).
  • The dosage schema of 1.2 g /kg bolus infusion followed by lower dose of 0.3 g / kg infusion may create sustained elevation in Vitamin C plasma levels for increased cytotoxic effect.
  • The addition of HDIVC & oral supplementation of Vitamin C to standard treatment with gemcitabine may improve quality of life for patients with comparison to prior to treatment start of this protocol.
  • CA 19-9 and inflammatory markers may show trends for patients in this trial.

Condition Intervention Phase
Metastatic Adenocarcinoma of the Pancreas
Drug: Gemcitabine, Intravenous and oral Ascorbic Acid (Vitamin C)
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Safety and Efficacy of Standard Dose Gemcitabine Combined With High Dose Intravenous Vitamin C (HDIVC) Treatment for Patients With Metastatic Adenocarcinoma of the Pancreas.

Resource links provided by NLM:


Further study details as provided by Eastern Regional Medical Center:

Primary Outcome Measures:
  • Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Weekly for up to 6 months. ] [ Designated as safety issue: Yes ]
    Adverse events, whether volunteered by the study subject, discovered by the investigators during questioning, or detected by physical examination, laboratory tests, or other means will be collected and recorded at each visit. Events will be recorded from the time the consent is signed until 4 weeks after the study protocol is discontinued. Subjects experiencing Grade 4 neutropenia, Grade ≥3 thrombocytopenia, or Grade 2 peripheral neuropathy who do not recover will have treatment protocol discontinued.


Secondary Outcome Measures:
  • Anti-Tumor Response [ Time Frame: Every 2 months for up to 6 months. ] [ Designated as safety issue: No ]
    CT and PET scans will be performed at baseline and then every two months. Target and Non-Target Lesions will be identified and recorded at baseline. When subsequent scans are performed, anti-tumor responses will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST).


Enrollment: 3
Study Start Date: June 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HDIVC
Gemcitabine (Gemzar), Intravenous and oral Ascorbic Acid (Vitamin C).
Drug: Gemcitabine, Intravenous and oral Ascorbic Acid (Vitamin C)
Weeks 1,2,3: IV Gemcitabine 1000 mg / m² over 30 minutes followed by HDIVC 1.2 g / kg: 1.2 g/kg over 90 minutes for a dose ≤90 g and over 120 minutes for a dose >90g followed by 0.3 g / kg over 120 minutes; Week 4: no treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient ≥ 18 years of age
  • Biopsy proven adenocarcinoma of the pancreas
  • Evidence of metastatic disease
  • Received at least 1 prior chemotherapy treatment regimen with disease progression
  • May have had any prior chemotherapy regimen including any gemcitabine based regimen or FOLFIRINOX
  • May have participated in a prior study protocol
  • May have had prior treatment with HDIVC
  • Anticipated survival of at least 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status = 0,1, or 2
  • The patient must have screening laboratory: ANC ≥ 1,500/mm3, Hemoglobin > 8g/dL, Platelets ≥ 100,000/mm3, Total Bilirubin < 1.5mg/dL, Creatinine ≤ 1.5mg/dL, Transaminases < 2.5 x upper limit of normal, Urine Uric Acid < 1.000 mg/d, Urine pH < 6, Urine microscopic negative for oxalates (if positive, reflex urinary oxalates < 60mg/d), PT INR ≤ 1.5, unless patient is on full dose warfarin
  • Glucose-6-phosphate dehydrogenase deficiency (G6PD) normal status via blood test The fluorescent spot test is the simplest, most reliable, and most sensitive of the G6PD screening tests
  • Willingness to undergo central line placement and able to manage care of the entry site safely
  • Willingness to adhere to supplemental oral dose regimen of ascorbic acid 500mg taken twice daily
  • All other nutritional supplements would be discontinued for the duration of the trial except for pancreatic enzymes and probiotics
  • Patients must be able to take food orally or have a peg tube for feeding
  • Able to give consent for protocol participation

Exclusion Criteria:

  • Glucose-6-phosphate dehydrogenase deficiency (G6PD)
  • Renal insufficiency : serum creatinine of > 1.5 mg /dl or evidence of oxalosis by urinalysis prior to enrollment and prior to each HDIVC infusion
  • Documentation or report of history of kidney stones or urinary oxalosis.
  • Co-morbid condition that would affect survival: congestive heart failure, unstable angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars of > 300 mg / dl, patients with known chronic active hepatitis or cirrhosis
  • Currently active second malignancy
  • Chronic hemodialysis
  • Iron overload/ Hemochromatosis: Ferritin > 500 ng / ml
  • Wilson's disease
  • Pregnant or lactating female (pre- menopausal females will undergo pregnancy test prior to administration of protocol drugs throughout treatment cycles during this study)
  • Aspirin use exceeding 81 mg per day
  • Acetaminophen use exceeding 2 g per day
  • Known brain metastasis
  • Active tobacco smokers
  • Treatment with the combination of HDIVC and gemcitabine previously
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01654861

Locations
United States, Pennsylvania
Eastern Regional Medical Center
Philadelphia, Pennsylvania, United States, 19124
Sponsors and Collaborators
Eastern Regional Medical Center
Investigators
Principal Investigator: Eiko Klimant, MD, FACP Eastern Regional Medical Center
Principal Investigator: Heather Wright, ND, FABNO Eastern Regional Medical Center
  More Information

No publications provided

Responsible Party: Eastern Regional Medical Center
ClinicalTrials.gov Identifier: NCT01654861     History of Changes
Other Study ID Numbers: ERMC 11-11
Study First Received: July 13, 2012
Last Updated: June 26, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Ascorbic Acid
Gemcitabine
Vitamins
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antioxidants
Antiviral Agents
Enzyme Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014