Adenocarcinoma, Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms, Pancreatic Neoplasms
Conditions
Keywords
Ascorbate, Vitamin C, Pharmacological ascorbate, Pharmacologic ascorbate, Ascorbic Acid, gemcitabine, nab-paclitaxel, Gemzar, Abraxane
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.
Interventions
DRUGGemcitabine
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
DRUGnab-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
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
Sponsors
University of Iowa
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Holden Comprehensive Cancer Center
McGuff Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Every 2 months until death from any cause, up to approximately 69 months. | Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause or until trial completion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Every 2 months to date of progression, up to approximately 69 months. | 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. |
| Tumor Response | Every 2 months for up to 10 years | 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. |
Countries
United States
Contacts
STUDY_DIRECTORJoseph J. Cullen, MD, FACS
University of Iowa
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.5 year |
| ECOG Performance status (PS) PS 0: Fully active, no restrictions | 8 Participants |
| ECOG Performance status (PS) PS 1: Restricted in physically strenuous activity | 11 Participants |
| ECOG Performance status (PS) PS 2: Ambulatory and capable of all selfcare but unable to carry out any work activities | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 34 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 16 | 18 / 18 |
| other Total, other adverse events | 16 / 16 | 18 / 18 |
| serious Total, serious adverse events | 10 / 16 | 10 / 18 |
Outcome results
None listed