Pancreatic NeoplasmsPhase 2NCT02905578
A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)
A Phase 2 study testing Gemcitabine, nab-paclitaxel and Pharmacological ascorbate in people with Pancreatic Neoplasms and Cancer of Pancreas, run by University of Iowa at 1 site in United States.
Trial summary
This clinical trial adds high-dose ascorbate (vitamin C) to the standard of care regimen for metastatic pancreatic adenocarcinoma (a type of pancreatic cancer). Subjects are randomized between a control group (standard treatment) and an intervention group (pharmacologic ascorbate in addition to the standard treatment). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Neoplasms, Cancer of Pancreas, Cancer of the Pancreas
- What is being tested?
- Gemcitabine, nab-paclitaxel and Pharmacological ascorbate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2018to 26 Aug 2024
- Phase
- Phase 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
- Pathologic diagnosis (cell samples, biopsy, brushing, surgical sample) of adenocarcinoma of the pancreas. Cancer from the Ampullae of Vater is also eligible. The tissue sample can be from a metastatic location, like a lymph node.
- Metastatic or node positive disease
- One cancer site, that did not receive radiation therapy, that is at least 1 cm in size when looking at it by CT scan (CAT scan)
- Recommended to receive gemcitabine and nab-paclitaxel
- Failed initial therapy or be ineligible for definitive curative therapy (e.g., surgical excision, radiation therapy)
- A platelet count of at least 100,000 cells per mL
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- A creatinine level of less than 1 1/2 times the upper limit of normal for the local lab test, or, a creatinine clearance of at least 60 mL/(min*1.73m2)
- Not pregnant
- Commit to using birth control during the study (all participants)
Who cannot join
- Prior chemotherapy to treat the metastatic disease
- Other therapy (including radiation) within the past 4 weeks
- Side effects from prior therapies that are still deemed moderate to severe by a physician
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Patients actively receiving insulin or who are currently recommended to receive insulin by a doctor
- Patients requiring daily finger-stick blood glucose measurements
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- Patients who are on the following drugs and cannot have a substitution (or who decline the substitution):
- warfarin
- flecainide
- methadone
- amphetamines
- quinidine
- chlorpropamide
- An active cancer, other than the pancreatic cancer, that requires treatment.
- Enrolled in another therapeutic clinical trial
- Uncontrolled, intercurrent illness
- HIV positive individuals undergoing therapy due to known drug:drug interaction between antiretroviral drugs and high-dose ascorbate therapy
- Women who are nursing
Trial locations and contacts
1 site in 1 country.
United States1 site
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
About this study
Official title: A Phase II Trial of Pharmacological Ascorbate, Gemcitabine, and Nab-Paclitaxel for Metastatic Pancreatic Cancer (PACMAN 2.1)
This clinical trial adds high-dose ascorbate (vitamin C) to the standard of care regimen for metastatic pancreatic adenocarcinoma (a type of pancreatic cancer). Subjects are randomized between a control group (standard treatment) and an intervention group (pharmacologic ascorbate in addition to the standard treatment).
Read the detailed description
One of the standard treatments for metastatic pancreatic adenocarcinoma is nab-paclitaxel with gemcitabine. This standard therapy administers chemotherapy once per week for three weeks; patients then get a 'rest week' to complete the cycle (1 cycle = 4 weeks).
This study adds 75 grams of ascorbate (vitamin C, sometimes called pharamcological ascorbate because the dose is so high) to standard therapy. The ascorbate is administered intravenously - through a vein in the arm.
Participants in the control group will:
- receive gemcitabine and nab-paclitaxel chemotherapy, which is standard for their cancer.
- undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays
Participants in the intervention group will:
- receive 75 grams of ascorbate 3 times per calendar week for each week of the chemotherapy cycle.
- undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays
- provide blood samples to determine the biological effects, if any, the ascorbate has on the body during therapy.
This active therapy portion lasts until the disease progresses and a new treatment needs to be adopted - this can be months to years. If disease progresses, participants go back to standard follow-up for their caner and the new/additional therapy their doctors prescribe.
However, it is very important we remain in contact with participants; they will have life-long follow-up for this study.
- Conditions
- Pancreatic Neoplasms, Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms
- Being tested
- Gemcitabine, nab-paclitaxel, Pharmacological ascorbate
- Keywords
- Ascorbate, Vitamin C, Pharmacological ascorbate, Pharmacologic ascorbate, Ascorbic Acid, gemcitabine, nab-paclitaxel, Gemzar, Abraxane
- Medical subject headings
- Pancreatic Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar, Gemcitabine Hydrochloride
Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after nab-paclitaxel and before ascorbate
- given for 3 weeks out of the 4 week cycle
- standard dose reductions are used
- up to 2 cycles are administered before standard of care CT scan
- decision to continue therapy is based disease response to therapy as measured from the CT scan
- treatment continues until disease progression is identified
nab-paclitaxelDrug
Also called Abraxane
Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after before gemcitabine and ascorbate
- given for 3 weeks out of the 4 week cycle
- standard dose reductions are used
- up to 2 cycles are administered before standard of care CT scan
- decision to continue therapy is based disease response to therapy as measured from the CT scan
- treatment continues until disease progression is identified
Pharmacological ascorbateDrug
Also called Ascorbate, Vitamin C, Ascorbic acid
Administered intravenously the same day as nab-paclitaxel and gemcitabine Administered after nab-paclitaxel and gemcitabine
- given 3 times weekly
- given for 4 weeks out of the 4 week cycle
- no dose reductions are used
- up to 2 cycles are administered before standard of care CT scan
- decision to continue therapy is based disease response to therapy as measured from the CT scan
- treatment continues until disease progression is identified
| Study group | Role | What they receive |
|---|---|---|
| Ascorbate group | Experimental | Each cycle is 4 calendar weeks
Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Pharmacological ascorbate: 75 grams, three times weekly for 4 weeks Receives: Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: Pharmacological ascorbate |
| Control | Active comparator | Each cycle is 4 calendar weeks
Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Each cycle has 1 rest week Receives: Drug: Gemcitabine; Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause or until trial completion.
Measured: Every 2 months until death from any cause, up to approximately 69 months.
Secondary outcomes (2)
Progression Free Survival
Time, measured in months, it takes disease to progress, where disease progression is defined by the RECIST criteria (v1.1). Timeframe is from treatment day 1 to date of disease progression or until trial closure.
Measured: Every 2 months to date of progression, up to approximately 69 months.
Tumor Response
Determine the objective response rate of the disease, assessed every 2 months using CT or MRI, and evaluated/defined using the RECIST criteria (v1.1). Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.
Measured: Every 2 months for up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2016 (estimated)
- Study start28 Nov 2018
- Primary completion26 Aug 2024
- Study completion26 Aug 2024
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 (3)Papers the sponsor has linked to this study.
- Other trials for Pancreatic NeoplasmsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI), Holden Comprehensive Cancer Center, McGuff Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, John M. Buatti, University of Iowa
- Investigators
- Joseph J. Cullen, MD, FACS, Study director, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02905578
- Sponsor's protocol ID
- 201801759
- Other IDs
- 3P30CA086862, 5U01CA140206, P01CA217797
- Status last verified
- Jun 2026
- First submitted
- 14 Sep 2016
- Last updated
- 23 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared per consent document, governing Federal regulations and institutional policies, and only after a signed sharing agreement between the sponsor and the requesting investigator.
Publications
Doskey CM, Buranasudja V, Wagner BA, Wilkes JG, Du J, Cullen JJ, Buettner GR. Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy. Redox Biol. 2016 Dec;10:274-284. doi: 10.1016/j.redox.2016.10.010. Epub 2016 Oct 28.
PubMed 27833040Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Schultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR, Allen BG. O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017 Apr 10;31(4):487-500.e8. doi: 10.1016/j.ccell.2017.02.018. Epub 2017 Mar 30.
PubMed 28366679Bodeker KL, Smith BJ, Berg DJ, Chandrasekharan C, Sharif S, Fei N, Vollstedt S, Brown H, Chandler M, Lorack A, McMichael S, Wulfekuhle J, Wagner BA, Buettner GR, Allen BG, Caster JM, Dion B, Kamgar M, Buatti JM, Cullen JJ. A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol. 2024 Nov;77:103375. doi: 10.1016/j.redox.2024.103375. Epub 2024 Oct 2.
PubMed 39369582