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

University of Iowa40 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Interventions

GemcitabineDRUG

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

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

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Overall Survival

Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause or until trial completion.

Time frame: Every 2 months until death from any cause, up to approximately 69 months.

Secondary Outcomes

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.

Time frame: 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.

Time frame: Every 2 months for up to 10 years