Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Ascorbate, Ascorbic acid, Vitamin C, NSCLC, Non Small Cell Lung Cancer, carboplatin, paclitaxel
Brief summary
This clinical trial evaluates adding high-dose ascorbate (vitamin C) to standard of care treatment of non-small cell lung cancer (NSCLC) in adults. All subjects will receive high-dose ascorbate in addition to the standard treatment.
Detailed description
Standard treatment for non-small cell lung cancer (NSCLC) involves a combined therapy of paclitaxel and carboplatin. These drugs are administered once every 21 days. This study adds high dose ascorbic acid (75g per infusion) twice per week for up to 4 cycles of therapy. Participants will: * receive high doses of intravenous (IV) ascorbate two times a week during each 3 week chemotherapy. * have blood samples drawn to measure blood ascorbate levels once every 21 days * have blood samples drawn to measure iron and ferritin levels before treatment, then on cycles 1 and 3. The active therapy portion of this study lasts for 4 months. After that is completed, participants will go back to standard therapy for their cancer. Participants will continue to have life-long follow-up for this study.
Interventions
DRUGPaclitaxel
* Administered intravenously (IV) * Prescribed at 200 mg/m2 (standard dose) * Given once every 21 days (i.e., one cycle) * Up to 4 cycles are administered depending on disease response
DRUGCarboplatin
* Administered intravenously (IV) * Prescribed at AUC = 6 using the Cockcroft-Gault formula (standard dose) * Given once every 21 days (i.e., one cycle) * Up to 4 cycles are administered depending on disease response
DRUGAscorbic Acid
* Administered intravenously (IV) * 75g per infusion * Two infusions per week * 1 cycle is 3 weeks * given up to 4 cycles * may be given while chemotherapy if delayed due to low counts
Sponsors
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Holden Comprehensive Cancer Center
McGuff Pharmaceuticals, Inc.
Joseph J. Cullen, MD, FACS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* newly diagnosed stage IIIB or IV non -small cell lung cancer. The potential participant must not have received first-line cytotoxic therapy. Prior use of first-line EGFR inhibitors or ALK inhibitors is allowed if there was progression on therapy. * CNS metastasis is allowed if the metastasis is treated and there are no signs of progression following treatment. The potential participant must be off steroids for at least 3 days and be stable. * At least 18 years of age * ECOG performance status of 0, 1, or 2 * absolute neutrophil count (ANC) of at least 1500 cells per mm³ * platelet count of at least 100,000 cells per mm³ * hemoglobin of at least 8 g/dL * creatinine within 1.5 times the upper limit of normal * total bilirubin within 1.5 times the upper limit of normal * ALT within 3 times the institutional upper limit of normal * AST within 3 times the institutional upper limit of normal * the participant must tolerate a 15g ascorbate test infusion (screening dose) * patients who received prior treatment with curative intent must have experienced a treatment-free interval of at least 6 months since the last treatment * the participant must not be pregnant, be willing to have a pregnancy test done if deemed necessary, and be willing to use adequate birth control during the study * not breastfeeding * independently able to provide consent (legally authorized representative and/or power of attorney is not allowed)
Exclusion criteria
* known sensitizing EGFR mutations or ALK gene rearrangements if the participant has not yet tried EGFR or ALK inhibitor therapies. If the potential participant's biopsy did not allow for gene analysis (inconclusive, not enough tissue), the patient is considered eligible for the study. Enrollment on this clinical trial after progression on targeted therapy is allowed * 50% or greater PD-L1 expression (patients with unknown PD-L1 expression or when PD-L1 expression can't be determined due to insufficient tumor sample or other reasons remain eligible) * receiving warfarin therapy and cannot tolerate drug substitution * active hemoptysis within 1 week of screening (more than 1/2 teaspoon of blood per day) * actively receiving insulin at the time of ascorbate infusion * G6PD deficiency * leptomeningeal disease * potential participants cannot be on the following drugs: flecainide, methadone, amphetamines, quinidine, or chlorpropamide. * known active invasive malignancy other than the lung cancer under therapy (non-melanoma skin cancer or carcinoma in situ of the cervix or bladder are exempted) * potential participants may not enroll in, or be actively receiving treatment from, a therapeutic clinical trial for their cancer. Observational studies (including imaging studies) are acceptable. * uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements * known HIV positive individuals cannot be enrolled in this trial because high-dose ascorbate is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | every 2 months for up to 5 years post treatment | From cycle 1, day 1, to documented disease progression in CT imaging as described by RECIST criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | every 2 months for up to 5 years post treatment | The time (in months) it takes for disease to progress as defined by RECIST criteria. Timeframe will be from cycle 1, day 1 to date of progression. |
| Overall Survival (OS) | every 2 months for up to 5 years post treatment | Time, measured in months, from cycle 1 day 1 until date of death from any cause |
Countries
United States
Participant flow
Recruitment details
Enrollment was between April 2015 through November 2020
Participants by arm
| Arm | Count |
|---|---|
| Ascorbate, Paclitaxel, Carboplatin Paclitaxel, administered once per cycle (3 weeks) Carboplatin, administered once per cycle (3 weeks) Pharmacological ascorbate (ascorbic acid) infusions, 2 times per week for 3 weeks
Paclitaxel: - Administered intravenously (IV)
* Prescribed at 200 mg/m2 (standard dose)
* Given once every 21 days (i.e., one cycle)
* Up to 4 cycles are administered depending on disease response
Carboplatin: - Administered intravenously (IV)
* Prescribed at AUC = 6 using the Cockcroft-Gault formula (standard dose)
* Given once every 21 days (i.e., one cycle)
* Up to 4 cycles are administered depending on disease response
Ascorbic Acid: - Administered intravenously (IV)
* 75g per infusion
* Two infusions per week
* 1 cycle is 3 weeks
* given up to 4 cycles
* may be given while chemotherapy if delayed due to low counts | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Ascorbate, Paclitaxel, Carboplatin |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 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 | 36 Participants |
| Region of Enrollment United States | 38 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 31 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 18 / 40 |
Outcome results
Primary
Tumor Response
From cycle 1, day 1, to documented disease progression in CT imaging as described by RECIST criteria
Time frame: every 2 months for up to 5 years post treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ascorbate, Paclitaxel, Carboplatin | Tumor Response | unevaluable | 1 Participants |
| Ascorbate, Paclitaxel, Carboplatin | Tumor Response | confirmed partial response | 13 Participants |
| Ascorbate, Paclitaxel, Carboplatin | Tumor Response | stable disease | 19 Participants |
| Ascorbate, Paclitaxel, Carboplatin | Tumor Response | progressive disease | 5 Participants |
Secondary
Overall Survival (OS)
Time, measured in months, from cycle 1 day 1 until date of death from any cause
Time frame: every 2 months for up to 5 years post treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ascorbate, Paclitaxel, Carboplatin | Overall Survival (OS) | 12.8 months |
Secondary
Progression Free Survival (PFS)
The time (in months) it takes for disease to progress as defined by RECIST criteria. Timeframe will be from cycle 1, day 1 to date of progression.
Time frame: every 2 months for up to 5 years post treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ascorbate, Paclitaxel, Carboplatin | Progression Free Survival (PFS) | 5.7 months |