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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: nab-paclitaxel
* Drug: Pharmacological ascorbate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ascorbate group<br>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 | Drug: Gemcitabine<br>* 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<br>* Other names: Gemcitabine Hydrochloride;Drug: nab-paclitaxel<br>* 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<br>* Other names: Abraxane;Drug: Pharmacological ascorbate<br>* 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<br>* Other names: Ascorbic acid;|
| Active Comparator: Control<br>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 | Drug: Gemcitabine<br>* 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<br>* Other names: Gemcitabine Hydrochloride;Drug: nab-paclitaxel<br>* 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<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ascorbate, Vitamin C, Pharmacological ascorbate, Pharmacologic ascorbate, Ascorbic Acid, gemcitabine, nab-paclitaxel, Gemzar, Abraxane