Trial of Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) (AA NABPLAGEM)
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|ClinicalTrials.gov Identifier: NCT03410030|
Recruitment Status : Active, not recruiting
First Posted : January 25, 2018
Last Update Posted : August 20, 2021
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Cancer Pancreas Cancer Pancreatic Adenocarcinoma Resectable Pancreatic Ductal Adenocarcinoma Pancreas Metastases||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 :||27 participants|
|Intervention Model:||Single Group Assignment|
|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|
|Actual Study Start Date :||December 15, 2017|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||June 30, 2022|
Experimental: Ascorbic Acid
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
Drug: Ascorbic Acid
Drug: Paclitaxel protein-bound
- Phase IB: Recommended Phase II dose (to give ≥ 20 mM) of ascorbic acid for Phase II [ Time Frame: approximately 63 days ]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
- Phase II: Disease control rate (CR+PR+SD x18 weeks) [ Time Frame: approximately 63 days ]To determine the preliminary efficacy (Disease control rate of CR+ PR+SD X 18 weeks) of the combination of high dose ascorbic acid (AA) at MTD with triple therapy of nanoparticle albumin- bound paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer.
- Incidence of toxicities [ Time Frame: approximately 63 days ]Lab testing will be completed to evaluate standard of care labs for subject safety
- Percent of patients who normalize their CA19-9 [ Time Frame: approximately 63 days ]Lab testing will be completed to evaluate normalization of CA19-19
- overall survival [ Time Frame: approximately 12 weeks from last study treatment ]Telephone followup will be conducted every 12 weeks from the last dose of treatment to determine survival status
- Progression free [ Time Frame: approximately 12 weeks from last study treatment ]Telephone followup will be conducted every 12 weeks from the last dose of treatment to determine status of disease progression
- Changes in patient's self-reported quality of life [ Time Frame: approximately 63 days ]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: approximately 63 days ]Changes in patient's self-reported pain levels will be determined by administering the Brief Pain Inventory (BPI)
- Tumor texture on radiologic scans [ Time Frame: approximately 63 days ]Imaging will be completed to evaluate tumor texture on radiologic scans as a non-invasive imaging biomarker for response, biologic, pathologic and outcome measures
- Correlation between peak plasma concentration of ascorbic acid and response to treatment [ Time Frame: approximately 63 days ]Lab testing will be completed to evaluate the correlation between peak plasma concentration of ascorbic acid and response to treatment
- Potential tumor biomarkers [ Time Frame: approximately 63 days ]Tumor biopsy testing will be completed to evaluate potential biomarkers in the tumor including tumor immune cell infiltration, stromal activation, stem cell enumeration, metabolic profiles, whole exome and whole genome CN, ChIP-seq/ATAQ seq, IHC and PCR assays on immune cell populations, CAFs, stem cell content (CD133, Aldh) and Musashi
- Potential blood biomarkers [ Time Frame: approximately 63 days ]Lab testing will be completed to evaluate potential biomarkers in the blood samples. Test may include CTCs/circCSC enumeration, Single CTC/circCSC transcription profiling, immune profiling [CD4+CD8+ T cells, MDSC (IDO-1+HLR-DR-/lowCD33+CD11b+CD14+), Immunosuppressive plasmocytes (CD19+CD138+IgA+IL-10+PD-L1+), Th17 (CD3+gdTCR+IL-17A+), Treg (CD4+Foxp3+), Hypo-responsive NK cells (CD3-CD56+KIR-NKG2A-), cfDNA, GPC1+ exosomes.
- Changes in circulating tumor stem cells [ Time Frame: approximately 63 days ]Lab testing will be completed to evaluate changes in numbers of circulating tumor stem cells and macrophage lineage changes
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): NCT03410030
|United States, Arizona|
|HonorHealth Research Institute|
|Scottsdale, Arizona, United States, 85258|
|Principal Investigator:||Gayle S Jameson, RN, MSN, ACNP-BC, AOCN||HonorHealth Research Institute|