Metastatic Adenocarcinoma of the Pancreas
Conditions
Brief summary
* 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.
Interventions
DRUGGemcitabine, 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.
Sponsors
Eastern Regional Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events as a Measure of Safety and Tolerability | Weekly for up to 6 months. | 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
| Measure | Time frame | Description |
|---|---|---|
| Anti-Tumor Response | Every 2 months for up to 6 months. | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HDIVC Gemcitabine (Gemzar), Intravenous and oral Ascorbic Acid (Vitamin C).
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. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | HDIVC |
|---|---|
| Age, Continuous | 55 years |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Adverse Events as a Measure of Safety and Tolerability
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.
Time frame: Weekly for up to 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HDIVC | Adverse Events as a Measure of Safety and Tolerability | 0 participants |
Secondary
Anti-Tumor Response
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).
Time frame: Every 2 months for up to 6 months.
Population: Data were not analyzed as the study was prematurely closed.