Colorectal Cancer, Lung Cancer, Pancreatic Cancer
Conditions
Brief summary
This is a multicenter, single arm, 3-cohort, open-label trial of high dose Vitamin C intravenous infusion in subjects with solid tumor malignancies who are eligible for resection (cohort A) or with extended RAS (e.g.KRAS or NRAS) or BRAF mutation metastatic cancer who have received prior systemic treatment (cohort B). Cohort C will involve patients with colorectal cancer having an extended RAS or BRAF mutation who are amenable for localregional therapy of hepatic metastases with Yttrium-90 radioembolization.
Detailed description
This clinical trial is for men and women with resectable or metastatic solid tumor malignancies. The objective of the study is to investigate whether high dose vitamin C infusion leads to pathological tumor response in resectable colorectal, pancreatic, and lung cancer (cohort A) or objective tumor response in KRAS or BRAF mutant solid tumors (cohort B). For Cohort C, the primary objective is to determine that maximal tolerated dose of the combination of high dose vitamin C with Y90 radioembolization for patients solid tumor malignancies and liver metastases amenable to local-regional therapy Patients in cohort A receive a high dose vitamin C infusion for 4 days per week for 2-4 consecutive weeks prior to surgery. Patients in cohort B receive high dose vitamin C infusion for 4 days per week for up to 6 months or disease progression. Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day. A tumor sample will be resected after completion of study drug (high dose vitamin C infusion) treatment to examine the effects of study drug (Cohort A only). In addition, organoids will be grown in vitro and continue to be treated with vitamin C added in culture medium to examine tumor response. The resected tumor in this study will Key eligibility: * Men and women age 18 and older * Patients with histologically proven early stage or locally advanced colorectal adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection, and have not received chemotherapy or radiotherapy (cohort A) Patients with inoperable, metastatic, KRAS or BRAF mutant colorectal adenocarcinoma, lung cancer and pancreatic cancer, who have received at least 1 line of treatment for metastatic disease (cohort B) * Patients with metastatic cancer with an extended RAS (e.g. KRAS or NRAS) or BRAF mutation with liver metastases amenable to Y90 radioembolization (cohort C).
Interventions
DRUGVitamin C
Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day.
Sponsors
Stand Up To Cancer
Weill Medical College of Cornell University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 18 years of age. * Patients with histologically proven early stage or locally advanced colorectal adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection (cohort A). * Patients with inoperable, metastatic extended RAS (e.g. KRAS or NRAS) or BRAF mutant colorectal adenocarcinoma, lung cancer and pancreatic cancer, or other solid tumor, who have received at least 1 line of treatment for metastatic disease (cohort B). * Patients with metastatic cancer with an extended RAS (e.g. KRAS or NRAS) or BRAF mutation with liver metastases amenable to Y90 radioembolization (cohort C). * ECOG performance status 0-1. * Life expectancy of at least 6 months. * All women of child-bearing potential and all sexually active male patients must agree to use effective contraception.
Exclusion criteria
* Patients with uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (Appendix B: New York Heart Association (NYHA) Classifications). * Patients with active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV) (Appendix B: New York Heart Association (NYHA) Classifications). * Patients who have received an investigational drug within 21 days of the first dose of study drug. * Patients who are pregnant or lactating. * Patients who are known to be positive for the human immunodeficiency virus (HIV). The effect of Vitamin C on HIV medications is unknown. Note: HIV testing is not required for eligibility, but if performed previously and was positive, the patient is ineligible for the study. * Patient who are receiving drugs which are known to interact with Vitamin C, potential risk and eligibility will be evaluated individually by the investigator. a. Most of the known interactions with vitamin C are from oral use and acidification of the stomach lining. There are few known interactions with high dose intravenous vitamin C. We recommend not using deferoxamine as there may be an association with ventricular dysfunction (unknown mechanism). * Patients who have uncontrolled or severe hyponatremia, hypernatremia, SIADH, hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia * Patients who have uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding. * Patients who require therapeutic doses of warfarin * Patients who have uncontrolled seizure disorder, ascites, iron overload, edema, or dehydration. * Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, or other conditions predisposing patient to hemolysis. * Patients who have a known history of recurrent oxalate renal calculi or multiple oxalate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response Based on Tumor Regression Grading in Cohort A Patients | cohort A - 8 weeks | Number of patients with partial or complete pathological response in surgically resected tumor tissue: Pathological response rate is the number of patients with partial or complete pathological response in surgically resected tumor tissue. Pathologic response was assessed by tumor regression grade. This is a pathologic assessment of the amount of residual cancer cells in the specimen and the degree of fibrosis in the sample specimen. A completer response is 0% residual cancer cells. A partial response is 10-50% residual cancer cells, and no response is \>50% residual cancer cells within the tumor specimen. |
| Maximal Tolerated Dose of High Dose Vitamin C in Combination With Y90 Radioembolization | Cohort C - 16 weeks | Maximal tolerated dose will be evaluated by assessment of dose limiting toxicities for multiple dose levels. Dose limiting toxicity will be defined as any grade 3-4 adverse event possibly, probably, or definitely attributed to vitamin C therapy in the 21 days of protocol therapy. In any group of 3 patients, if one patient experiences dose limiting toxicity, the group will be expanded by 3 additional patients (eg. 6 for that group). If, at any dose level, 2 or more patients experience a dose limiting toxicity, the maximal tolerated dose will be reached, and further dose escalation will not be pursued. The dose level may then be expanded up to 10 additional patients to confirm the safety and toxicity at that dose level. |
| 3-month Disease Control Rate (DCR) Will be Evaluated Using RECIST v 1.1 in Cohort B Patients. | Cohort B - 3 months | Percentage of patients with complete response, partial response, or stable disease as a result of their therapy at 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Adverse events were assessed from the start of study treatment to 30 days after the last infusion of vitamin C. For Cohort A and C, this was approximately 2 months. For Cohort B this was about a 6 month duration. | The number of participants per cohort who experienced a Grade 3 or 4 adverse event (as defined by CTCAE v4.03) that was deemed possibly, probably, or definitely related to Vitamin C. |
| Maximum Concentration of Vitamin C in Hours in Cohort B | Up to 24 hours post-infusion | The serum concentration of vitamin C was serially measured following vitamin C infusion at 1.25 g/kg at various timepoints up to 24 hours post infusion to determine the maximum concentration (Cmax) in mM. |
| Time to Maximum Concentration and Half-life of Vitamin C (t1/2) in Hours in Cohort B | Up to 24 hours post-infusion | The serum concentration of vitamin C was serially measured following vitamin C infusion at 1.25 g/kg at various timepoints up to 24 hours post infusion to determine the Tmax and t(1/2) in hours |
| Progression-free Survival (PFS) | cohort B - up to 6 months | PFS is defined as the time from registration to cancer progression or death due to any cause for up to 6 months. Cancer progression is defined using the Response Evaluation Criteria in Solid Tumors v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in non-target lesions, or the appearance of new lesions. |
| Objective Response Rate (ORR) | cohort B - up to 6 months cohort C - 16 weeks | Number of patients with a partial response or complete response based on RECIST 1.1 Criteria. |
Other
| Measure | Time frame | Description |
|---|---|---|
| In Vitro Activity of Vitamin C in Tumor Organoids | cohort A - 8 weeks, cohort B - up to 6 months | Molecular signature of vitamin C efficacy will be determined using RNA sequencing and compared between KRAS or BRAF mutant vs wild type tumors. Organoids will be prepared from resected tumor samples and treated with vitamin C. |
| Pharmacodynamic Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol. | cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks | Immunohistochemical (IHC) staining for GLUT1 protein expression will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues. Immunohistochemical (IHC) staining for phosphor-AMPK will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues to assess AMPK activation. |
| Exploratory Biomarker Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol | cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks | To explore potential correlation of gene expression pattern with anti-tumor activity of vitamin C, we plan to perform RNA sequencing using surgical sample in cohort A patients who will receive vitamin C infusion pre-operatively. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Vitamin C + Surgery Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks.
Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day. | 7 |
| Cohort B: Vitamin C Only Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for up to 6 months.
Vitamin C: Vitamin C infusion will be administered intravenously at 1.25 g/kg for 4 days per week for 2-4 consecutive weeks (cohort A) or up to 6 months (cohort B). Cohort C will receive high dose vitamin C for 1-3 weeks. During week 1 vitamin C infusion and Y90 radioembolization of hepatic metastases will occur same day. | 21 |
| Cohort C: Vitamin C + Y-90 Dose Level 1 Vitamin C will be administered at a dose of 0.5 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. | 3 |
| Cohort C: Vitamin C + Y-90 Dose Level 2 Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. | 3 |
| Cohort C: Vitamin C + Y-90 Dose Level 3 Vitamin C will be administered at a dose of 0.75 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. | 4 |
| Cohort C: Vitamin C + Y-90 Dose Level 4 Vitamin C will be administered at a dose of 1 g/kg intravenously for 4 days /week for 1-2 weeks prior to and following Y90 therapy for a total of 4 weeks of vitamin C. A single dose of Vitamin C at 0.5g/kg will also be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. | 3 |
| Cohort C: Vitamin C + Y-90 Dose Level 5 A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. | 3 |
| Cohort C: Vitamin C + Y-90 Dose Level 6 A single dose of Vitamin C at 0.75g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. | 7 |
| Cohort C: Vitamin C + Y-90 Dose Level 7 A single dose of Vitamin C at 1g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. | 3 |
| Cohort C: Vitamin C + Y-90 Dose Level 8 A single dose of Vitamin C at 1.25g/kg will be administered on the day of Y90 radioembolization, administered prior to or within 24 hours of a Y90 treatment. Vitamin C will also be administered at a dose of 1.25 g/kg intravenously for 4 days/week for 1-2 weeks following Y90 therapy. | 7 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | COVID Precautions | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Started New Treatment | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A: Vitamin C + Surgery | Total | Cohort C: Vitamin C + Y-90 Dose Level 8 | Cohort C: Vitamin C + Y-90 Dose Level 7 | Cohort C: Vitamin C + Y-90 Dose Level 6 | Cohort C: Vitamin C + Y-90 Dose Level 5 | Cohort C: Vitamin C + Y-90 Dose Level 4 | Cohort C: Vitamin C + Y-90 Dose Level 3 | Cohort C: Vitamin C + Y-90 Dose Level 2 | Cohort C: Vitamin C + Y-90 Dose Level 1 | Cohort B: Vitamin C Only |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 49.02 years | 61.66 years | 58.94 years | 69.92 years | 58.05 years | 77.73 years | 48.46 years | 75.66 years | 55.5 years | 54.51 years | 60.72 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 10 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 50 Participants | 7 Participants | 2 Participants | 7 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 6 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) White | 5 Participants | 44 Participants | 5 Participants | 2 Participants | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 14 Participants |
| Region of Enrollment United States | 7 participants | 61 participants | 7 participants | 3 participants | 7 participants | 3 participants | 3 participants | 4 participants | 3 participants | 3 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 31 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 30 Participants | 5 Participants | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 1 / 21 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 3 | 2 / 7 | 0 / 3 | 1 / 7 |
| other Total, other adverse events | 6 / 7 | 18 / 19 | 3 / 3 | 3 / 3 | 3 / 4 | 3 / 3 | 3 / 3 | 7 / 7 | 2 / 3 | 5 / 6 |
| serious Total, serious adverse events | 0 / 7 | 4 / 19 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 3 | 4 / 7 | 0 / 3 | 2 / 6 |
Outcome results
Primary
3-month Disease Control Rate (DCR) Will be Evaluated Using RECIST v 1.1 in Cohort B Patients.
Percentage of patients with complete response, partial response, or stable disease as a result of their therapy at 3 months
Time frame: Cohort B - 3 months
Population: DCR was not collected for Cohort A or Cohort C. 5 participants from Cohort B were missing scans and were therefor unevaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Vitamin C + Surgery | 3-month Disease Control Rate (DCR) Will be Evaluated Using RECIST v 1.1 in Cohort B Patients. | 1 Participants |
Primary
Maximal Tolerated Dose of High Dose Vitamin C in Combination With Y90 Radioembolization
Maximal tolerated dose will be evaluated by assessment of dose limiting toxicities for multiple dose levels. Dose limiting toxicity will be defined as any grade 3-4 adverse event possibly, probably, or definitely attributed to vitamin C therapy in the 21 days of protocol therapy. In any group of 3 patients, if one patient experiences dose limiting toxicity, the group will be expanded by 3 additional patients (eg. 6 for that group). If, at any dose level, 2 or more patients experience a dose limiting toxicity, the maximal tolerated dose will be reached, and further dose escalation will not be pursued. The dose level may then be expanded up to 10 additional patients to confirm the safety and toxicity at that dose level.
Time frame: Cohort C - 16 weeks
Population: Only patients that received a dose of Vitamin C in Cohort C were considered evaluable. In Cohort C, 30 out of 32 participants who received vitamin C were evaluated across dose levels. Cohort A and B were not dose escalations, and therefore were not evaluated for maximum tolerated dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Vitamin C + Surgery | Maximal Tolerated Dose of High Dose Vitamin C in Combination With Y90 Radioembolization | Vitamin C Weekly Infusion Dose | 1.25 g/kg |
| Cohort A: Vitamin C + Surgery | Maximal Tolerated Dose of High Dose Vitamin C in Combination With Y90 Radioembolization | Vitamin C Infusion Dose the Day of Y-90 Radioembolization | 1.25 g/kg |
Primary
Pathologic Response Based on Tumor Regression Grading in Cohort A Patients
Number of patients with partial or complete pathological response in surgically resected tumor tissue: Pathological response rate is the number of patients with partial or complete pathological response in surgically resected tumor tissue. Pathologic response was assessed by tumor regression grade. This is a pathologic assessment of the amount of residual cancer cells in the specimen and the degree of fibrosis in the sample specimen. A completer response is 0% residual cancer cells. A partial response is 10-50% residual cancer cells, and no response is \>50% residual cancer cells within the tumor specimen.
Time frame: cohort A - 8 weeks
Population: Only the 6 patients who had surgery from Cohort A, and thus had evaluable tissue, were analyzed for this measure. Participants in Cohort B and C did not undergo surgery, and were thus not evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Vitamin C + Surgery | Pathologic Response Based on Tumor Regression Grading in Cohort A Patients | 1 Participants |
Secondary
Maximum Concentration of Vitamin C in Hours in Cohort B
The serum concentration of vitamin C was serially measured following vitamin C infusion at 1.25 g/kg at various timepoints up to 24 hours post infusion to determine the maximum concentration (Cmax) in mM.
Time frame: Up to 24 hours post-infusion
Population: Pharmacokinetics were not assessed for Cohort A and C. PK samples for 5 participants from Cohort B were not obtained and therefore only 16/21 participants were evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: Vitamin C + Surgery | Maximum Concentration of Vitamin C in Hours in Cohort B | 41.19 mM | Standard Deviation 10.89 |
Secondary
Objective Response Rate (ORR)
Number of patients with a partial response or complete response based on RECIST 1.1 Criteria.
Time frame: cohort B - up to 6 months cohort C - 16 weeks
Population: For Cohort B, only 16/21 participants had complete sets of imaging scans and were therefore evaluable. Participants in Cohort A were not evaluated for ORR. In Cohort C Dose Level 3, one patient withdrew from the study early and therefore was unevaluable. For cohort C dose level 6, three patients did not have complete imaging to be evaluable. For Cohort C Dose Level one participant withdrew prior to treatment and one participant was missing scans, therefore they were not unevaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Vitamin C + Surgery | Objective Response Rate (ORR) | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Objective Response Rate (ORR) | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Objective Response Rate (ORR) | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Objective Response Rate (ORR) | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Objective Response Rate (ORR) | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Objective Response Rate (ORR) | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Objective Response Rate (ORR) | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Objective Response Rate (ORR) | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Objective Response Rate (ORR) | 0 Participants |
Secondary
Progression-free Survival (PFS)
PFS is defined as the time from registration to cancer progression or death due to any cause for up to 6 months. Cancer progression is defined using the Response Evaluation Criteria in Solid Tumors v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in non-target lesions, or the appearance of new lesions.
Time frame: cohort B - up to 6 months
Population: Participants from Cohort A and Cohort C were not assessed for PFS. 5 participants were missing scans from Cohort B and were therefore unevaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Vitamin C + Surgery | Progression-free Survival (PFS) | 36 days |
Secondary
Safety of High Dose Vitamin C Administration Using CTCAE 4.03.
The number of participants per cohort who experienced a Grade 3 or 4 adverse event (as defined by CTCAE v4.03) that was deemed possibly, probably, or definitely related to Vitamin C.
Time frame: Adverse events were assessed from the start of study treatment to 30 days after the last infusion of vitamin C. For Cohort A and C, this was approximately 2 months. For Cohort B this was about a 6 month duration.
Population: Overall number of participants analyzed includes any participants that were enrolled in the study and received at least one dose of Vitamin C.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort A: Vitamin C + Surgery | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 3 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 2 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 2 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 1 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 2 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 3 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 4 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 5 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 6 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 3 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 7 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypokalemia | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hypertension | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Anemia | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Fatigue | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alanine Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Alkaline Phosphatase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Confusion | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Scrotal Pain | 1 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Syncope | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Generalized Muscle Weakness | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Blood Bilirubin Increased | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Aspartate Aminotransferase Increase | 0 Participants |
| Cohort C: Vitamin C + Y-90 Dose Level 8 | Safety of High Dose Vitamin C Administration Using CTCAE 4.03. | Hemolysis | 0 Participants |
Secondary
Time to Maximum Concentration and Half-life of Vitamin C (t1/2) in Hours in Cohort B
The serum concentration of vitamin C was serially measured following vitamin C infusion at 1.25 g/kg at various timepoints up to 24 hours post infusion to determine the Tmax and t(1/2) in hours
Time frame: Up to 24 hours post-infusion
Population: Pharmacokinetics data was not assessed for Cohort A or Cohort C. PK samples for 5 participants from Cohort B were not obtained and therefore only 16/21 participants were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Vitamin C + Surgery | Time to Maximum Concentration and Half-life of Vitamin C (t1/2) in Hours in Cohort B | T(max) | 2.28 hours | Standard Deviation 0.38 |
| Cohort A: Vitamin C + Surgery | Time to Maximum Concentration and Half-life of Vitamin C (t1/2) in Hours in Cohort B | t(1/2) | 6.46 hours | Standard Deviation 1.44 |
Other Pre-specified
Exploratory Biomarker Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol
To explore potential correlation of gene expression pattern with anti-tumor activity of vitamin C, we plan to perform RNA sequencing using surgical sample in cohort A patients who will receive vitamin C infusion pre-operatively.
Time frame: cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks
Other Pre-specified
In Vitro Activity of Vitamin C in Tumor Organoids
Molecular signature of vitamin C efficacy will be determined using RNA sequencing and compared between KRAS or BRAF mutant vs wild type tumors. Organoids will be prepared from resected tumor samples and treated with vitamin C.
Time frame: cohort A - 8 weeks, cohort B - up to 6 months
Other Pre-specified
Pharmacodynamic Samples From Tumor Tissue Will be Collected at the Time Points Specified in the Protocol.
Immunohistochemical (IHC) staining for GLUT1 protein expression will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues. Immunohistochemical (IHC) staining for phosphor-AMPK will be performed on Formalin Fixed Paraffin Embedded (FFPE) tumor tissues to assess AMPK activation.
Time frame: cohort A - 8 weeks, cohort B - up to 6 months, Cohort C - 16 weeks