A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)

Pancreas Cancer Clinical Trial

Official title:

A Phase II Trial of Pharmacological Ascorbate, Gemcitabine, and Nab-Paclitaxel for Metastatic Pancreatic Cancer (PACMAN 2.1)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02905578
• Other study ID #: 201801759
• Secondary ID: 3P30CA0868625U01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 28, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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
• 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)

Exclusion Criteria:

• 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
• 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Cancer of Pancreas
• Cancer of the Pancreas
• Neoplasms
• Neoplasms, Pancreatic
• Pancreas Cancer
• Pancreas Neoplasms
• Pancreatic Neoplasms

Intervention

Drug:
• Gemcitabine
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-paclitaxel
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 ascorbate
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

Locations

Country	Name	City	State
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa

Sponsors (5)

Lead Sponsor	Collaborator
Joseph J. Cullen	Holden Comprehensive Cancer Center, McGuff Pharmaceuticals, Inc., National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

Du J, Cieslak JA 3rd, Welsh JL, Sibenaller ZA, Allen BG, Wagner BA, Kalen AL, Doskey CM, Strother RK, Button AM, Mott SL, Smith B, Tsai S, Mezhir J, Goswami PC, Spitz DR, Buettner GR, Cullen JJ. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer. Cancer Res. 2015 Aug 15;75(16):3314-26. doi: 10.1158/0008-5472.CAN-14-1707. Epub 2015 Jun 16. — View Citation

Schoenfeld 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. Erratum In: Cancer Cell. 2017 Aug 14;32(2):268. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause.	Every 2 months for up to 20 years post-treatment
Secondary	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.	Every 2 months for up to 10 years
Secondary	Progression free survival	Time, measured in days, it takes disease to progress, where disease progression is defined by the RECIST criteria (v1.1). Timeframe is from radiation day 1 to date of disease progression.	Every 2 months for up to 10 years
Secondary	Adverse event frequency and categorization	Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (CTCAE v4). Assessments will be monthly through 30 days past the end of therapy.	Monthly through 30 days after end of treatment.