Carcinoma, Non-Small-Cell Lung, Nonsmall Cell Lung Cancer, Non-Small Cell Lung Cancer, Non-Small-Cell Lung Carcinoma, NSCLC
Conditions
Keywords
pharmacological ascorbate, ascorbic acid, radiation, chemotherapy, carboplatin, paclitaxel
Brief summary
This clinical trial evaluates adding high-dose ascorbate (vitamin C) to a standard therapy for non-small cell lung cancer. The standard therapy is radiation therapy combined with carboplatin and paclitaxel (types of chemotherapy). All subjects will receive high-dose ascorbate in addition to the standard therapy.
Detailed description
For selected stages of non-small cell lung cancer (NSCLC), standard treatment involves radiation therapy and chemotherapy. The chemotherapy regimen typically used is paclitaxel and carboplatin. Both of these chemotherapeutic drugs are administered intravenously, using a vein in the arm. Radiation is administered using a machine external to the body (usually a linear accelerator). After combined therapy, NSCLC patients receive 2 extra cycles of chemotherapy, called "consolidation chemotherapy." This study adds 75 grams of ascorbate (vitamin C, sometimes called pharmacological ascorbate because the dose is so high) at specific timepoints in the therapy. The ascorbate is administered intravenously - through a vein in your arm. Participants will: * receive 75 grams of intravenous ascorbate 3 times per calendar week while they are receiving radiation therapy. The IV will be running while the radiation therapy is administered. * undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays. * provide blood samples to determine the biological effects, if any, the ascorbate has on the body during therapy This active therapy portion lasts for about 10 to 12 weeks. After that is done, participants go back to standard follow-up for their cancer and any additional therapy their doctors believe they need. However, it is very important the investigators remain in contact with participants; they will have life-long follow-up for this study.
Interventions
DRUGRadiation Therapy
Conformal radiation administered daily, Monday through Friday Total dose is 60 Gray (Gy) and is delivered in 2 Gy fractions. One fraction is delivered daily for a total of 30 fractions in 30 days
DRUGPaclitaxel
Administered intravenously (IV) Given the same day as carboplatin, but given before the carboplatin is administered * the dose is 45 mg/m2 (standard dose) * Administered weekly * 6 to 7 weeks of therapy, depending on when radiation starts * Standardized dose reductions are used
DRUGCarboplatin
Administered intravenously (IV) GIven the same day as paclitaxel, immediately after the paclitaxel infusion is done. * Prescribed at area-under-the-curve (AUC) = 2 using the Cockroft-Gault formula (standard) * Administered weekly * 6 to 7 weeks of therapy, depending on when radiation starts * Standard dose reductions are used
DRUGAscorbic Acid
Administered intravenously * 75 grams per infusion; each infusion is about 2 hours * 3 infusion per calendar week * The infusion is actively running for at least 20 minutes when radiation begins * May be given while chemotherapy is delayed due to low counts * Dose reductions are not used * Given for 6 to 7 weeks, depending on when radiation starts
Sponsors
Joseph J. Cullen, MD, FACS
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Holden Comprehensive Cancer Center
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
Note: patients who have a small pleural effusion that is too small to safety tap and is not visible on a chest x-ray are still eligible * Pathologic diagnosis (i.e., cell sample, biopsy, tissue swap, bronchoscopy) of non-small cell lung cancer. * Recommended to receive carboplatin \& paclitaxel with radiation therapy as a treatment * Tumor or metastatic disease must measure at least 1 cm using a CT scan (CAT scan) * Physician determined the patient is healthy enough for chemotherapy and radiation therapy * At least part of the lung cancer must be viewable and measurable by CT or MRI * A platelet count of at least 100,000 cells per mililiter * A creatinine level of less than 1 1/2 times the upper limit of normal for the local lab test, or, a creatinine clearance of at least 60 mL/(min\*1.73m2) * Not pregnant, and commit to using birth control during the study
Exclusion criteria
* Exudative pleural effusion * Recurrent non-small cell lung cancer * Glucose-6-phosphate dehydrogenase (G6PD) deficiency * Patients actively receiving insulin or patients whose doctors have recommended current insulin use * Patients requiring daily finger-stick blood glucose measurements * Patients who are on the following drugs and cannot have a substitution or who decline the substitution: * warfarin * flecainide * methadone * amphetamines * quinidine * chlorpropamide * Prior radiation therapy that would result in a field overlap * Enrolled in another therapeutic clinical trial * Uncontrolled, intercurrent illness * Lactating women * HIV positive individuals undergoing therapy due to known drug:drug interaction between antiretroviral drugs and high-dose ascorbate therapy If all the above are met, the potential participant will receive a 15 gram challenge dose of ascorbate via intravenous infusion. This is the final screening procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Rate at the Completion of Radiation and Chemotherapy | 3 to 4 weeks after last radiation treatment | The proportion of participants with progressive disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at the completion of radiation and chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | Every six months for up to 20 years post-treatment | From radiation day 1 to documented disease progression as described by RECIST criteria. Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST. |
| Progression Free Survival (PFS) | Every six months for up to 20 years post-treatment | Time, measured in days, it takes for disease to progress, where disease progression is defined by the RECIST criteria (v1.1). Timeframe is from radiation day 1 to date of disease progression |
| Overall Survival (OS) | Every three months for up to 20 years post-treatment | Time, measured in months, from start of radiation to death from any cause. |
| Adverse Event Frequency and Categorization | Weekly for the first 7 weeks, then monthly for 3 months, then every 6 months through 2 years post-treatment | Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (CTCAE, v 4) as follows: * Through radiation, weekly assessment of adverse events * Consolidation chemotherapy, assessment day 1 of each cycle * Post-treatment, every 6 months through 2 years post-therapy |
Countries
United States
Contacts
STUDY_DIRECTORJoseph J Cullen, MD, FACS
University of Iowa
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 43 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 20 / 43 |
| other Total, other adverse events | 42 / 43 |
| serious Total, serious adverse events | 23 / 43 |
Outcome results
None listed