High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have Metastatic Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT03697239|
Recruitment Status : Withdrawn (FDA indicated the same study could not be conducted under multiple INDs)
First Posted : October 5, 2018
Last Update Posted : June 11, 2019
The purpose of this study is to see if 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.
Vitamin C is a nutrient found in food and dietary supplements. It protects cells and also plays a key role in making collagen (which provides strength and structure to skin, bones, tissues and tendons). High-dose vitamin C may be given by intravenous (IV) infusion (through a vein into the bloodstream) or orally (taken by mouth). When taken by intravenous infusion, vitamin C can reach much higher levels in the blood than when the same amount is taken by mouth. Some human studies of high-dose IV vitamin C in patients with cancer have shown improved quality of life, as well as improvements in physical, mental, and emotional functions, symptoms of fatigue, nausea and vomiting, pain, and appetite loss. Intravenous high-dose ascorbic acid has caused very few side effects in clinical trials.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Pancreatic Cancer Pancreatic Cancer Pancreas Cancer Pancreatic Adenocarcinoma Resectable Pancreatic Ductal Adenocarcinoma Pancreatic Metastasis||Drug: Ascorbic Acid Drug: Paclitaxel protein-bound Drug: Cisplatin Drug: Gemcitabine||Phase 1 Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine|
|Masking:||None (Open Label)|
|Official Title:||Phase IB/II Trial of High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have No Prior Therapy for Their Metastatic Pancreatic Cancer|
|Estimated Study Start Date :||June 2019|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2022|
Experimental: AA NABPLAGEM
ascorbic acid paclitaxel protein-bound cisplatin gemcitabine
Drug: Ascorbic Acid
25, 37.5, 56.25 or 75 grams/m2
Other Name: Vitamin C
Drug: Paclitaxel protein-bound
125mg/m2 over 30 minute IV infusions on days 1 and 8 repeated every 21 days
25mg/m2 in 500*mL of NS over 60minute IV infusion on days 1 and 8 repeated every 21 days
1000mg/m2 in 500*mL over 30 minute IV infusion on days 1 and 8 repeated every 21 days
- Maximum tolerated dose (MTD) [ Time Frame: 18 weeks ]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
- Disease Control Rate [ Time Frame: 18 weeks ]CR+ PR+SD
- Incidence of Treatment-Emergent Grade 2-5 Adverse Events assessed using NCI CTCAE v5.0 toxicity criteria [ Time Frame: 18 weeks ]
- Percent of patients who normalize their CA19-9 [ Time Frame: 18 weeks ]Lab testing will be completed to evaluate normalization of CA19-19
- Progression free survival (PFS) [ Time Frame: approximately 12 weeks from last study treatment ]Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine status of disease progression
- Overall survival (OS) [ Time Frame: approximately 12 weeks from last study treatment ]Telephone follow up will be conducted every 12 weeks from the last dose of treatment to determine survival status
- Changes in patient's self-reported quality of life [ Time Frame: 18 weeks ]Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory (MDASI-GI)
- Changes in patient's self-reported pain levels [ Time Frame: 18 weeks ]Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory (MDASI-GI)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03697239
|United States, California|
|UC San Diego Moores Cancer Center|
|La Jolla, California, United States, 92093|
|Principal Investigator:||Hitendra Patel, MD||University of California, San Diego|