Trial of Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM)

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Total Dose Received [Identifying Recommended Maximum Tolerated Dose (MTD)] [From enrollment through end of treatment, up to 40 weeks]. Mean, Dose (g/m^2) (Standard Deviation). Ascorbic Acid 25 g/m^2 (n=6): 235.3 (66.3); Ascorbic Acid 37.5 g/m^2 (n=4): 410.4 (62.0); Ascorbic Acid 56.25 g/m^2 (n=7): 589.1 (135.7).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Duration of Dose in Days [Identifying Recommended Maximum Tolerated Dose (MTD)] [From enrollment through end of treatment, up to 40 weeks]. Mean, Days (Standard Deviation). Ascorbic Acid 25 g/m^2 (n=6): 235.5 (51.9); Ascorbic Acid 37.5 g/m^2 (n=4): 165.9 (51.4); Ascorbic Acid 56.25 g/m^2 (n=7): 149.0 (54.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Incidence of Toxicities [From enrollment through 30 days after the end of treatment, up to 40 weeks]. Mean, count of adverse event term (Standard Deviation). 25 g/m2: Ascorbic Acid (n=17): 4.0 (3.4). 37.5 g/m2: Ascorbic Acid (n=17): 3.0 (1.4). 56.25 g/m2: Ascorbic Acid (n=17): 3.1 (2.3).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Normalization of Tumor Markers by AA Treatment Group [From enrollment through study completion, up to 40 weeks]. Count Of Participants, Participants. CA 19-9 Normalized: Ascorbic Acid 25g/m^2 (n=5): 1; Ascorbic Acid 37.5 gm^2 (n=3): 0; Ascorbic Acid 56.25 g/m^2 (n=6): 3. CEA Normalized: Ascorbic Acid 25g/m^2 (n=5): 1; Ascorbic Acid 37.5 gm^2 (n=3): 0; Ascorbic Acid 56.25 g/m^2 (n=6): 0. CA-125 Normalized: Ascorbic Acid 25g/m^2 (n=5): 3; Ascorbic Acid 37.5 gm^2 (n=3): 1; Ascorbic Acid 56.25 g/m^2 (n=6): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival [Approximately 12 weeks from last study treatment, assessed up to 3 years]. Median, months (95% Confidence Interval). Ascorbic Acid 25 g/m2 (n=6): 14.2 (5.0 to NA) [The upper bound of the confidence interval cannot be estimated due to an insufficient number of participants with events.]; Ascorbic Acid 37.50 gm/m2 (n=4): 7.7 (2.5 to NA) [The upper bound of the confidence interval cannot be estimated due to an insufficient number of participants with events.]; Ascorbic Acid 56.25 gm/m2 (n=7): 15.9 (2.4 to NA) [The upper bound of the confidence interval cannot be estimated due to an insufficient number of participants with events.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival [Approximately 12 weeks from last study treatment, assessed up to 3 years]. Median, months (95% Confidence Interval). Ascorbic Acid 25 g/m2 (n=6): 8.9 (3.6 to NA) [The upper bound of the confidence interval cannot be estimated due to an insufficient number of participants with events.]; Ascorbic Acid 37.50 gm/m2 (n=4): 6.4 (2.1 to NA) [The upper bound of the confidence interval cannot be estimated due to an insufficient number of participants with events.]; Ascorbic Acid 56.25 gm/m2 (n=7): 5.7 (1.5 to 10.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Quality of Life: MD Anderson's Symptom Inventory-GI (MDASI-GI) [From Cycle 1 to end of treatment, up to 40 weeks]. Mean, MDASI-GI Score (Standard Deviation). Start of Cycle 1: Ascorbic Acid 25 g/m2 (n=6): 1.8 (0.8 to 2.5); Ascorbic Acid 37.50 gm/m2 (n=4): 3.7 (1.6 to 6.9); Ascorbic Acid 56.25 gm/m2 (n=7): 1.9 (0.6 to 2.1). End of Treatment (EOT): Ascorbic Acid 25 g/m2 (n=6): 0.8 (0.4); Ascorbic Acid 37.50 gm/m2 (n=4): 1.4 (0.8); Ascorbic Acid 56.25 gm/m2 (n=7): 1.5 (2.0).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Quality of Life: Brief Pain Inventory (BPI) - Pain Intensity (PI) [From start of Cycle 1 to end of treatment, up to 40 weeks]. Mean, BPI-PI Score (Standard Error). Start of Cycle 1: Ascorbic Acid 25 g/m2 (n=6): 1.90 (1.8); Ascorbic Acid 37.50 gm/m2 (n=4): 3.5 (1.2); Ascorbic Acid 56.25 gm/m2 (n=7): 2.4 (1.9). End of Treatment (EOT): Ascorbic Acid 25 g/m2 (n=6): 0.7 (0.9); Ascorbic Acid 37.50 gm/m2 (n=4): 3.0 (1.1); Ascorbic Acid 56.25 gm/m2 (n=7): 0.9 (1.9).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Duration of Dose in Weeks [Identifying Recommended Maximum Tolerated Dose (MTD)] [From enrollment through end of treatment, up to 40 weeks]. Mean, Weeks (Standard Deviation). Ascorbic Acid 25 g/m^2 (n=6): 33.6 (7.4); Ascorbic Acid 37.5 g/m^2 (n=4): 23.7 (7.3); Ascorbic Acid 56.25 g/m^2 (n=7): 21.3 (7.7).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Disease Control Rate (CR+PR+SD at 18 Weeks) [18 weeks]. Number, Percentage of participants (95% Confidence Interval). Ascorbic Acid 25 g/m2 (n=6): 83.3 (35.9 to 99.6); Ascorbic Acid 37.50 gm/m2 (n=4): 75.0 (19.4 to 99.4); Ascorbic Acid 56.25 gm/m2 (n=7): 57.1 (9.9 to 81.6).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Best Overall Response [From enrollment through end of treatment, up to 36 weeks]. Count Of Participants, Participants. Complete Response (CR): Ascorbic Acid 25 g/m2 (n=6): 0; Ascorbic Acid 37.50 gm/m2 (n=4): 0; Ascorbic Acid 56.25 gm/m2 (n=7): 0. Partial Response (PR): Ascorbic Acid 25 g/m2 (n=6): 5; Ascorbic Acid 37.50 gm/m2 (n=4): 3; Ascorbic Acid 56.25 gm/m2 (n=7): 3. Stable Disease (SD): Ascorbic Acid 25 g/m2 (n=6): 1; Ascorbic Acid 37.50 gm/m2 (n=4): 0; Ascorbic Acid 56.25 gm/m2 (n=7): 2. Progressive Disease (PD): Ascorbic Acid 25 g/m2 (n=6): 0; Ascorbic Acid 37.50 gm/m2 (n=4): 1; Ascorbic Acid 56.25 gm/m2 (n=7): 2.