Pancreatic CancerPhase 1/2AA NABPLAGEMNCT03410030

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

A Phase 1/2 study testing High Dose Ascorbic Acid 25 g/m^2, Nanoparticle Paclitaxel protein bound 125mg/m^2 and Cisplatin 25mg/m^2 in people with Pancreatic Cancer and Pancreas Cancer, run by HonorHealth Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Pancreatic Cancer, Pancreas Cancer, Pancreatic Adenocarcinoma Resectable
What is being tested?: High Dose Ascorbic Acid 25 g/m^2, Nanoparticle Paclitaxel protein bound 125mg/m^2 and Cisplatin 25mg/m^2
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteUnited States
Study dates: 15 Dec 2017to 6 Sep 2023
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must meet the following criteria to be included in the trial:
Be willing and able to provide written informed consent/assent for the trial.
Be ≥ 18 years of age on day of signing informed consent.
Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with measurable disease according to RECIST 1.1 criteria).
Have a performance status of 0 or 1 on the ECOG performance scale.
Demonstrate adequate organ function as defined below in table 4. All screening labs should be performed within 14 days of treatment initiation.

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Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving first dose of study medication.
Female participants of childbearing potential must be willing to use adequate method of contraception (as outlined in section 4.4.2) for the duration of the trial.
Male participants must agree to use adequate contraception (as outlined in section 4.4.2) for the duration of the trial.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.

Who cannot join

Patients must not meet any of the following criteria in order to be eligible for the trial:
Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment.
Exposure to any investigational agent within 4 weeks prior to initiation of study treatment.
Patients who need constant use of finger stick blood glucose monitoring for tight contro l of their diabetes being the ascorbic acid causes false low readings of glucose via that technology (Vasudevan and Hirsch 2014) 39
Any person with a G6PD deficiency

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History of renal oxalate stones (if type of stone is unknown, need to assess urine oxalates level if >60mg/dL, then patient is not eligible for the study)
Patient is taking acetaminophen at any dose, or any medication that contains acetaminophen within 72 hours of first dose of ascorbic acid.
Hypersensitivity to any of the agents proposed for treatment.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through one week from the last dose of trial treatment.
Patients with evidence of iron overload, defined as a transferrin saturation > 45 percent AND serum ferritin > 200 ng/mL (males) or >150 ng/mL (females).
Current, serious, clinically significant cardiac arrhythmias as determined by the investigator, or patient receiving a digitalis derivative.

Trial locations and contacts

1 site in 1 country.

United States1 site

HonorHealth Research Institute
Scottsdale, Arizona, 85258

Other trials in United States

About this study

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

Read the detailed description

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.

Conditions: Pancreatic Cancer, Pancreas Cancer, Pancreatic Adenocarcinoma Resectable, Pancreatic Ductal Adenocarcinoma, Pancreas Metastases
Being tested: High Dose Ascorbic Acid 25 g/m^2, Nanoparticle Paclitaxel protein bound 125mg/m^2, Cisplatin 25mg/m^2, Gemcitabine 1000mg/m^2, High Dose Ascorbic Acid 37.5 g/m^2
Medical subject headings: Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

High Dose Ascorbic Acid 25 g/m^2Drug
Also called AA
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle
Nanoparticle Paclitaxel protein bound 125mg/m^2Drug
Also called Abraxane
30 minute IV infusions on days 1 and 8 repeated every 21 days
Cisplatin 25mg/m^2Drug
Also called Platinol
Via 500mL of Normal Saline over 60 minute IV infusion on days 1 and 8 repeated every 21 days
Gemcitabine 1000mg/m^2Drug
Also called Gemzar
Via 500mL of Normal Saline over 30 minute IV infusion on days 1 and 8 repeated every 21 days
High Dose Ascorbic Acid 37.5 g/m^2Drug
Also called AA
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle
High Dose Ascorbic Acid 56.25 g/m^2Drug
Also called AA
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle
High Dose Ascorbic Acid 75 g/m^2Drug
Also called AA
2x per week IV infusion Normal Saline on days Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle

Study groups in NCT03410030
Study group	Role	What they receive
High Dose Ascorbic Acid 25 g/m^2	Experimental	25 grams/m^2 of ascorbic acid via infusion at the rate of 0.5 - 1.0 grams/minute (max). Infusions will occur two times per week administered prior to chemotherapy during weeks 1 \& 2 and on intervening weeks of a 21-day cycle. Approximate days for ascorbic acid infusion will be Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle. Receives: Drug: High Dose Ascorbic Acid 25 g/m^2; Drug: Nanoparticle Paclitaxel protein bound 125mg/m^2; Drug: Cisplatin 25mg/m^2; Drug: Gemcitabine 1000mg/m^2
High Dose Ascorbic Acid 37.5 g/m^2	Experimental	37.5 g/m^2 of ascorbic acid via infusion at the rate of 0.5 - 1.0 grams/minute (max). Infusions will occur two times per week administered prior to chemotherapy during weeks 1 \& 2 and on intervening weeks of a 21-day cycle. Approximate days for ascorbic acid infusion will be Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle. Receives: Drug: Nanoparticle Paclitaxel protein bound 125mg/m^2; Drug: Cisplatin 25mg/m^2; Drug: Gemcitabine 1000mg/m^2; Drug: High Dose Ascorbic Acid 37.5 g/m^2
High Dose Ascorbic Acid 56.25 g/m^2	Experimental	56.25 g/m^2 of ascorbic acid via infusion at the rate of 0.5 - 1.0 grams/minute (max). Infusions will occur two times per week administered prior to chemotherapy during weeks 1 \& 2 and on intervening weeks of a 21-day cycle. Approximate days for ascorbic acid infusion will be Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle. Receives: Drug: Nanoparticle Paclitaxel protein bound 125mg/m^2; Drug: Cisplatin 25mg/m^2; Drug: Gemcitabine 1000mg/m^2; Drug: High Dose Ascorbic Acid 56.25 g/m^2
High Dose Ascorbic Acid 75 g/m^2	Experimental	75 g/m^2 of ascorbic acid via infusion at the rate of 0.5 - 1.0 grams/minute (max). Infusions will occur two times per week administered prior to chemotherapy during weeks 1 \& 2 and on intervening weeks of a 21-day cycle. Approximate days for ascorbic acid infusion will be Day 1, 3, 8, 10, 15, and 17 of each 21-day cycle. Receives: Drug: Nanoparticle Paclitaxel protein bound 125mg/m^2; Drug: Cisplatin 25mg/m^2; Drug: Gemcitabine 1000mg/m^2; Drug: High Dose Ascorbic Acid 75 g/m^2

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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].
Measured: 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.
Measured: From enrollment through end of treatment, up to 36 weeks

Secondary outcomes (6)

Incidence of Toxicities
Incidence of adverse events reported according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Cycle 1 to end of treatment, up to 40 weeks
Quality of Life: Brief Pain Inventory (BPI) - Pain Intensity (PI)
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.
Measured: From start of Cycle 1 to end of treatment, up to 40 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Dec 20176 Sep 2023

First posted25 Jan 2018
Study start15 Dec 2017
Primary completion14 Sep 2021
Study completion6 Sep 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pancreatic CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Phase IB: 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: 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.
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03410030
Sponsor's protocol ID: SU2C HRI NPG-002
Acronym: AA NABPLAGEM
Status last verified: Aug 2025
First submitted: 9 Jan 2018
Last updated: 23 Jul 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: If the study site is a 'covered site' under the definitions of the Health Insurance Portability and Accounting Act (HIPAA), the Investigator will ensure that the patient consents to the use of data by HonorHealth and its designees for the purposes of regulatory submissions, study publications, and drug approval. SU2C will be notified of any outputs of the research such as guidelines, publications, presentation, changes in service delivery etc. prior to external submission or presentation. In any oral or written report or poster presentation of Results or otherwise relating to the Research, the support of CRUK, SU2C and the Lustgarten foundation will be acknowledged, displaying the relevant logs where possible. Any publications resulting from research funded in whole or in part by the Grant must be cited as required per signed confidentiality agreements.

Publications

Jameson GS, LeGrand SD, Gordon MS, Roe DJ, Wertheim BC, Olszewski K, Rabinowitz J, Evans R, Downes M, Truitt M, Korn R, Han H, Miller RM, Barrett MT, Propper D, Von Hoff DD, Borazanci E. Phase IB trial of high dose ascorbic acid + nab-paclitaxel + cisplatin + gemcitabine in patients with untreated metastatic pancreatic cancer. Redox Biol. 2025 Dec;88:103895. doi: 10.1016/j.redox.2025.103895. Epub 2025 Oct 25.
PubMed 41197185

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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