Bladder Cancer
Conditions
Keywords
Intravenous (IV) Ascorbic Acid (Vitamin C)
Brief summary
Bladder cancer is a common disease with high rates of mortality, especially at advanced stages. Neo-adjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy is considered standard of care for patients with muscle invasive disease, as NAC improves surgical outcomes in these patients. However, some patients are ineligible for cisplatin-based chemotherapy due to other medical issues. Although a combination of carboplatin and gemcitabine has been used with limited success, most patients proceed directly to cystectomy without realizing the potential survival benefit afforded by NAC. Intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve both carboplatin and gemcitabine-based therapy in other models. This trial will add IVC to gemcitabine/carboplatin chemotherapy to evaluate whether co-treatment will increase therapeutic efficacy.
Detailed description
see protocol
Interventions
DRUGAscorbic Acid
Ascorbic Acid Intravenous
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
To assess pathologic downstaging rate in MIBC cisplatinineligible patients when IVC is added to a gemcitabine/carboplatin NAC regimen.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status = 0 -- 2 * Cisplatin-ineligible, muscle invasive bladder cancer * Adequate organ and marrow functions * Women of child-bearing potential and men with partners of child-bearing potential must agree to use protocol specified forms of birth control
Exclusion criteria
* Patient simultaneously enrolled in any therapeutic clinical trial * Current or anticipated use of other investigational agents while participating in this study * Psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or breast feeding. There is a potential for congenital abnormalities and for this regimen to harm breast feeding infants * Histology of pure adenocarcinoma, pure squamous cell carcinoma, or pure small cell carcinoma in the TURBT sample * Prior systemic chemotherapy (prior intravesical therapy is allowed) and/ or prior radiation therapy to the urinary bladder * Uncontrolled intercurrent illness * Current consumption of tobacco products * History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post Treatment Pathological Staging | 6 weeks after first IVC infusion at radical cystectomy | Post treatment specimen pathology results evaluated per the WHO TNM staging system. The staging system is a qualitative assessment based on the results of the physical exam, biopsy, imaging tests, and the results of surgery. The earliest stage cancers are called stage 0 (or carcinoma in situ), and then range from stages I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means a more advanced cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Change in Patient-reported Quality of Life Outcomes | Baseline, End of Treatment (completion of neoadjuvant therapy, Day 28), Post-surgery (6 weeks post-operative) | Scores evaluated per Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) version 4 - quality of life (QOL) questionnaire scores: * FACT-Bl total score range is 0-156, derived by the sum of the sub-scales. Higher scores indicate better QOL. * FACT-Bl includes five sub-scales: * Physical Well-being (PWB), score range of 0-28 * Social/Family Well-being (SWB), score range of 0-28 * Emotional Well-being (EWB), score range of 0-24 * Functional Well-being (FWB), score range of 0-28 * Bladder Cancer Subscale (BlCS), score range of 0-48 * Note: Negatively stated items are reversed by subtracting the response from 4. |
| Disease Free Survival Rate (DFS) Among Participants | 5 years | DFS will be defined as time from cystectomy to disease recurrence or death resulting from disease. DFS represents time from random assignment to cancer recurrence or death from any cause. Patients alive without disease progression at the time of analysis were censored at the date of last disease assessment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV Ascorbic Acid IV Ascorbic Acid 25 grams (g) infused 2 times a week for 4 weeks
Ascorbic Acid: Ascorbic Acid Intravenous | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | IV Ascorbic Acid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 76.3 years STANDARD_DEVIATION 9.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 12 |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 2 / 12 |
Outcome results
Primary
Post Treatment Pathological Staging
Post treatment specimen pathology results evaluated per the WHO TNM staging system. The staging system is a qualitative assessment based on the results of the physical exam, biopsy, imaging tests, and the results of surgery. The earliest stage cancers are called stage 0 (or carcinoma in situ), and then range from stages I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means a more advanced cancer.
Time frame: 6 weeks after first IVC infusion at radical cystectomy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Ascorbic Acid | Post Treatment Pathological Staging | Stage II | 1 Participants |
| IV Ascorbic Acid | Post Treatment Pathological Staging | Stage 0 | 3 Participants |
| IV Ascorbic Acid | Post Treatment Pathological Staging | Stage I | 2 Participants |
| IV Ascorbic Acid | Post Treatment Pathological Staging | Stage III | 4 Participants |
| IV Ascorbic Acid | Post Treatment Pathological Staging | Stage IV | 2 Participants |
Secondary
Disease Free Survival Rate (DFS) Among Participants
DFS will be defined as time from cystectomy to disease recurrence or death resulting from disease. DFS represents time from random assignment to cancer recurrence or death from any cause. Patients alive without disease progression at the time of analysis were censored at the date of last disease assessment.
Time frame: 5 years
Secondary
Overall Change in Patient-reported Quality of Life Outcomes
Scores evaluated per Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) version 4 - quality of life (QOL) questionnaire scores: * FACT-Bl total score range is 0-156, derived by the sum of the sub-scales. Higher scores indicate better QOL. * FACT-Bl includes five sub-scales: * Physical Well-being (PWB), score range of 0-28 * Social/Family Well-being (SWB), score range of 0-28 * Emotional Well-being (EWB), score range of 0-24 * Functional Well-being (FWB), score range of 0-28 * Bladder Cancer Subscale (BlCS), score range of 0-48 * Note: Negatively stated items are reversed by subtracting the response from 4.
Time frame: Baseline, End of Treatment (completion of neoadjuvant therapy, Day 28), Post-surgery (6 weeks post-operative)