Stage IV Colorectal Cancer
Conditions
Keywords
Stage IV Colorectal cancer, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Ascorbic Acid, Vitamins, Irinotecan, Integrative Medicine, Complementary Medicine, Alternative Medicine Antioxidants, Molecular Mechanisms of Pharmacological Action, Pharmacologic Actions, Protective Agents, Physiological Effects of Drugs, Micronutrients, Growth Substances, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Therapeutic Uses, Radiation-Sensitizing Agents, Topoisomerase I Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors
Brief summary
This protocol is a phase I/II, study of ascorbic acid (AA) infusions combined with treatment with irinotecan versus treatment with irinotecan alone in patients with recurrent or advanced colorectal cancer who have failed at least one treatment regimen with a 5-FU based therapy. This study will be conducted as an amendment to Investigational New Drug # 77486.
Detailed description
Phase I: To assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated. This aim will be assessed by enrolling a minimum of 6 subjects meeting inclusion criteria, using a modified 3+3 design. Safety will be assessed with the following: toxicity graded by the NCI CTC, urinalysis pre- and post-infusion, basic metabolic panel, and CBC. From our experience and in the experience of our study collaborators, we hypothesize that the combination of IV AA with irinotecan will not be associated with adverse events. Phase II: To utilize CT or PET/CT (when available) scans to evaluate disease progression to assess overall tumor response rate (complete and partial response) in subjects with advanced or recurrent colorectal cancer treated with the combination of ascorbic acid and irinotecan versus irinotecan alone.
Interventions
DRUGAscorbic Acid
3x a week for 9 weeks
DRUGIrinotecan
350mg/m2 once a week every 3 weeks
Sponsors
Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Metastatic colorectal carcinoma (stage IV disease). * Patients must have progressed on one or more prior chemotherapy treatment regimens including at least one trial of a 5-FU/oxaliplatin based therapy (FOLFOX) in combination with bevacizumab. Patients must not have had standard chemotherapy within at least 2 weeks of beginning ascorbic acid treatment provided that they have recovered from any toxicities that they experienced. * G6PD status \> lower limit of normal * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. * Laboratory at baseline evaluation for inclusion in the study: creatinine ≤1.5X upper limit (if the creatinine is elevated, but ≤1.5X the ULN, a 24 hour creatinine clearance will be obtained); transaminase (AST/ALT) ≤2.0X upper limit of normal; bilirubin levels ≥ 2 mg/dL; ANC ≥1,500/mm3; Hemoglobin \> 8g/dL; platelet ≥ 100,000/mm3; * Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the study. * Willing and able to provide informed consent and participate in the study procedures.
Exclusion criteria
* Patients with evidence of a significant current psychiatric disorder that would prevent completion of the study as determined by the PI will not be allowed to participate. * Co-morbid medical condition that would affect survival or tolerance as determined by the PI. This includes patients who have not fully recovered from toxicities associated with prior therapy. It also includes subjects who, as determined by the PI, are at risk of experiencing fluid overload (i.e., congestive heart failure). * Patients who currently abuse alcohol or drugs. * Patients with known glomerular filtration rate of \<60ml/min or with nephrotic range proteinuria. * Pregnant or lactating women * Enrollment in active clinical trial/ experimental therapy or IND study within the prior 30 days. * Contraindication for CT or PET/CT as per the PI. * Patients who are on strong inducers of CYP3A4 which include but are not limited to: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Dexamethasone, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Experience Serious Adverse Events as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. | 9 weeks +/- 2 weeks | Safety: The primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Are Alive After 11 Weeks. | 9 weeks +/- 2 weeks | To evaluate progression-free survival related to treatment of patients with advanced or recurrent colorectal cancer |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ascorbic Acid+Irinotecan Ascorbic Acid (50-100g, 3x weekly)
Ascorbic Acid: 3x a week for 9 weeks | 4 |
| Standard of Care (Irinotecan Alone) 350mg/m2 once a week every 3 weeks | 0 |
| Total | 4 |
Baseline characteristics
| Characteristic | Ascorbic Acid+Irinotecan | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Region of Enrollment United States | 4 participants | 4 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 0 |
| other Total, other adverse events | 2 / 4 | 0 / 0 |
| serious Total, serious adverse events | 0 / 4 | 0 / 0 |
Outcome results
Primary
Number of Participants That Experience Serious Adverse Events as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Safety: The primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: 9 weeks +/- 2 weeks
Population: The study was closed early due to lack of accrual. The data were not collected or analyzed.
Secondary
Number of Participants That Are Alive After 11 Weeks.
To evaluate progression-free survival related to treatment of patients with advanced or recurrent colorectal cancer
Time frame: 9 weeks +/- 2 weeks
Population: The study was closed early due to lack of accrual. The data were not collected or analyzed.