The purpose of this study is to see if a treatment regimen with a combination of paclitaxel protein bound (also known as nab-paclitaxel), gemcitabine, and cisplatin when given with high dose Ascorbic Acid will be safe and effective in individuals with untreated metastatic pancreatic cancer.
Pancreatic cancer continues to be a very lethal disease. It was estimated that in 2016, 53,070 Americans would be diagnosed with pancreatic ductal adenocarcinoma (PDA), and 41,780 would die from the disease. This makes pancreatic cancer the third leading cause of death from cancer in the US. PDA is the twelfth most common cancer in the world with 338,000 new cases diagnosed in 2012. It is estimated that worldwide there will be \> 300,000 deaths from pancreatic cancer. Furthermore unfortunately PDA is projected to be the second leading cause of death from cancer in the US by 2030. Detection of pancreatic cancer has notoriously been very late in the disease and therefore the 5-year survival rate is only 8%, which is actually a slight improvement over the last few years. Right now the only potential cure for pancreatic cancer is surgical resection (if the disease is caught early). However only about 20% of PDA patients are eligible for potentially curable resection and unfortunately most (\> 80%) have recurrence of their cancer within 2 years of resection, and those recurrences are almost universally fatal. Recently it has been shown that there are regimens that actually improve survival for patients with advanced stage IV PDA. Conroy and colleagues have developed the Folfirinox regimen, which in a large randomized trial improved survival over gemcitabine as a single agent. Von Hoff and colleagues developed the nanoparticle albumin (nab) associated paclitaxel plus gemcitabine regimen which improved survival over single agent gemcitabine. Even more recently Jameson and colleagues have presented a combined regimen of nab-paclitaxel + gemcitabine + cisplatin in a small 24 patient phase Ib/II trial which showed a response rate of 71% with 2 patients having complete response, a 1-year survival of 65% and a median survival of 16+ months. While there have been multiple investigators and investigations into the use of ascorbic acid for patients with cancer (see ClinTrials.gov), its use has generally not been found to be of help for patients particularly when given orally - e.g. 10 grams daily.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle
30 minute IV infusions on days 1 and 8 repeated every 21 days
Via 500mL of Normal Saline over 60 minute IV infusion on days 1 and 8 repeated every 21 days
Via 500mL of Normal Saline over 30 minute IV infusion on days 1 and 8 repeated every 21 days
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle
HonorHealth Research Institute
Scottsdale, Arizona, United States
Total Dose Received [Identifying Recommended Maximum Tolerated Dose (MTD)]
To determine the maximum tolerated dose (MTD) of high dose ascorbic acid (AA) with triple therapy of nanoparticle paclitaxel protein bound+ cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer, the total dose received of ascorbic acid (g/m\^2) by participants was measured.
Time frame: From enrollment through end of treatment, up to 40 weeks
Duration of Dose in Days [Identifying Recommended Maximum Tolerated Dose (MTD)]
To determine the maximum tolerated dose (MTD) of high dose ascorbic acid (AA) with triple therapy of nanoparticle paclitaxel protein bound+ cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer, the duration of ascorbic acid dose in days is reported.
Time frame: From enrollment through end of treatment, up to 40 weeks
Duration of Dose in Weeks [Identifying Recommended Maximum Tolerated Dose (MTD)]
To determine the maximum tolerated dose (MTD) of high dose ascorbic acid (AA) with triple therapy of nanoparticle paclitaxel protein bound+ cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer, the duration of ascorbic acid dose in weeks is reported.
Time frame: From enrollment through end of treatment, up to 40 weeks
Disease Control Rate (CR+PR+SD at 18 Weeks)
Preliminary efficacy as measured by disease control rate (DCR), defined as the percentage of patients with complete response (CR) + partial response (PR) + stable disease (SD) at 18 weeks according to RECIST v1.1. CR = disappearance of all target lesions; PR = at least 30% decrease in sum of the longest diameters for target lesions, SD = insufficient change to qualify for PR or progressive disease \[defined as at least 20% increase in sum of the longest diameters for target lesions\].
Time frame: 18 weeks
Best Overall Response
Best overall response according to RECIST v1.1. Complete response (CR) = disappearance of all target lesions; Partial response (PD) = at least 30% decrease in sum of the longest diameters for target lesions; Stable disease (SD) = insufficient change to qualify for PR or PD; Progressive disease (PD) = at least 20% increase in sum of the longest diameters for target lesions.
Time frame: From enrollment through end of treatment, up to 36 weeks
Incidence of Toxicities
Incidence of adverse events reported according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: From enrollment through 30 days after the end of treatment, up to 40 weeks
Normalization of Tumor Markers by AA Treatment Group
The percentage of patients who had elevated levels of tumor marker CA 19-9 (or CA-125/CEA if not expressors of CA 19-9) and had their levels normalize. Elevated levels were defined as any value \>35 U/mL for CA 19-9, \>35 U/mL for CA-125, and \>3 ng/mL for CEA. Normalization was defined as any patient who had elevated tumor marker values at baseline and decreased to CA 19-9 value of 0.0-35 U/mL, CA-125 value of 0.0-35 U/mL, or CEA value of 0.0-3 ng/mL during treatment.
Time frame: From enrollment through study completion, up to 40 weeks
Overall Survival
Telephone follow-up conducted every 12 weeks from the last dose of treatment to determine survival status.
Time frame: Approximately 12 weeks from last study treatment, assessed up to 3 years
Progression-free Survival
Telephone follow-up conducted every 12 weeks from the last dose of treatment to determine status of disease progression.
Time frame: Approximately 12 weeks from last study treatment, assessed up to 3 years
Quality of Life: MD Anderson's Symptom Inventory-GI (MDASI-GI)
Changes in patient's self-reported quality of life as determined by administering the MD Anderson Symptom Inventory (MDASI-GI). This questionnaire asks patients to rank the severity of symptoms using a 0-10 scale (0 = not present to 10 = as bad as you can imagine) and averages the responses of 18 questions to produce an MDASI-GI score on a 0-10 scale. MDASI-GI scores measured at the start of Cycle 1 and at the end of treatment (EOT) are reported here.
Time frame: From Cycle 1 to end of treatment, up to 40 weeks
Quality of Life: Brief Pain Inventory (BPI) - Pain Intensity (PI)
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Changes in patient's self-reported pain levels determined by administering the Brief Pain Inventory (BPI) - Pain Intensity (PI) assessment. This questionnaire asks about pain intensity using a 0-10 scale (0 = not present to 10 = as bad as you can imagine) and averages the responses of 4 questions to output a BPI-PI score on a 0-10 scale. BPI-PI scores measured at the start of Cycle 1 and at the end of treatment (EOT) are reported here.
Time frame: From start of Cycle 1 to end of treatment, up to 40 weeks