Pancreatic Adenocarcinoma, Recurrent Pancreatic Carcinoma, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer, Unresectable Pancreatic Carcinoma
Conditions
Brief summary
This pilot clinical trial studies the side effects of ascorbic acid and combination chemotherapy in treating patients with pancreatic cancer that has spread to other places in the body, has come back, or cannot be removed by surgery. Nutrients found in food and dietary supplements, such as ascorbic acid, may improve the tolerability of chemotherapy regimens. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ascorbic acid and combination chemotherapy may work better in treating patients with pancreatic cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine safety of intravenous ascorbic acid in combination with fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX) as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 in patients with advanced pancreatic cancer. SECONDARY OBJECTIVES: I. To test feasibility of collecting quality of life (QOL), patient reported outcomes (PRO) data and correlative studies on patients with advanced pancreatic cancer.
Interventions
DRUGOxaliplatin
Given IV
DRUGIrinotecan Hydrochloride
Given IV
DRUGLeucovorin Calcium
Given IV
DRUGFluorouracil
Given IV
DIETARY_SUPPLEMENTAscorbic Acid
Given IV
Sponsors
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Capable of giving informed consent * Histological diagnosis of adenocarcinoma of the pancreas * Stage IV or recurrent pancreatic cancer by imaging * Locally advanced unresectable pancreatic cancer by National Comprehensive Cancer Network (NCCN) criteria * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 * No prior treatment for metastatic disease (prior neo-adjuvant or adjuvant chemotherapy, except FOLFIRINOX, chemoradiation or radiation allowed) * White blood count \>= 3000 * Platelets \>= 100,000 * Total bilirubin =\< 1.5 mg/dl * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 X upper limit of normal (ULN) * Creatinine \< 1.5 mg/dL * Glucose-6-phosphatase deficiency (G6PD) level of 5-14 units/g hemoglobin (Hgb) or within institutional standard parameters * All subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study
Exclusion criteria
* Other pancreatic cancer histology (islet cell, acinar, neuroendocrine tumors) * Resectable pancreatic cancer * Prior neoadjuvant FOLFIRINOX * Pregnant or lactating females * No clinical ascites (mild ascites on scans permissible) * Central nervous system (CNS) metastasis * Known congestive heart failure, significant ventricular arrhythmias, cirrhosis, grade 4/5 chronic kidney disease, uncontrolled diabetes * Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy * Peripheral neuropathy grade 2 or greater * Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as Determined by CTCAE Version 4.03 | Up to 28 days after the last treatment | After 4 patients are enrolled on the study and receive at least one dose of intravenous ascorbic acid, the data will be reviewed. If 2 out of the 4 cannot complete 2 courses of FOLFIRINOX then the study will be halted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life as Defined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 | Baseline to up to 28 days after the last treatment | Change in quality of life over the six measurement times will be modeled using mixed effects linear regression to account for correlation among repeated measurements from the same subjects. Average change in QoL from baseline to follow-up will be computed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (FOLFIRINOX, Ascorbic Acid) Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Oxaliplatin: Given IV
Irinotecan Hydrochloride: Given IV
Leucovorin Calcium: Given IV
Fluorouracil: Given IV
Ascorbic Acid: Given IV | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Treatment (FOLFIRINOX, Ascorbic Acid) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 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 | 3 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 | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 6 / 8 |
Outcome results
Primary
Number of Participants With Adverse Events as Determined by CTCAE Version 4.03
After 4 patients are enrolled on the study and receive at least one dose of intravenous ascorbic acid, the data will be reviewed. If 2 out of the 4 cannot complete 2 courses of FOLFIRINOX then the study will be halted.
Time frame: Up to 28 days after the last treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (FOLFIRINOX, Ascorbic Acid) | Number of Participants With Adverse Events as Determined by CTCAE Version 4.03 | Grade 4 adverse event | 1 Participants |
| Treatment (FOLFIRINOX, Ascorbic Acid) | Number of Participants With Adverse Events as Determined by CTCAE Version 4.03 | Grade 5 adverse event | 1 Participants |
| Treatment (FOLFIRINOX, Ascorbic Acid) | Number of Participants With Adverse Events as Determined by CTCAE Version 4.03 | Grade 3 adverse event | 4 Participants |
| Treatment (FOLFIRINOX, Ascorbic Acid) | Number of Participants With Adverse Events as Determined by CTCAE Version 4.03 | No Serious Adverse Events | 2 Participants |
Secondary
Change in Quality of Life as Defined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30
Change in quality of life over the six measurement times will be modeled using mixed effects linear regression to account for correlation among repeated measurements from the same subjects. Average change in QoL from baseline to follow-up will be computed.
Time frame: Baseline to up to 28 days after the last treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (FOLFIRINOX, Ascorbic Acid) | Change in Quality of Life as Defined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 | NA score on a scale |