Clinical trial NCT02905578: A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)
Official title: A Phase II Trial of Pharmacological Ascorbate, Gemcitabine, and Nab-Paclitaxel for Metastatic Pancreatic Cancer (PACMAN 2.1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Pancreatic Neoplasms
Cancer of Pancreas
Cancer of the Pancreas
Neoplasms, Pancreatic
Pancreas Cancer
Pancreas Neoplasms
Adenocarcinoma
Keywords: Ascorbate
Vitamin C
Pharmacological ascorbate
Pharmacologic ascorbate
Ascorbic Acid
gemcitabine
nab-paclitaxel
Gemzar
Abraxane
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
name: Holden Comprehensive Cancer Center
name: McGuff Pharmaceuticals, Inc.
First posted: 2016-09-19
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: Every 2 months for up to 20 years post-treatment
Secondary outcomes:
measure: Tumor Response
timeFrame: Every 2 months for up to 10 years
measure: Progression free survival
timeFrame: Every 2 months for up to 10 years
measure: Adverse event frequency and categorization
timeFrame: Monthly through 30 days after end of treatment.
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
Study officials:
affiliation: University of Iowa
name: Joseph J. Cullen, MD, FACS
role: STUDY_DIRECTOR
References:
citation: 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.
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.