Clinical trial NCT02905591: A Phase 2 Study Adding Ascorbate to Chemotherapy and Radiation Therapy for NSCLC
Official title: A Phase 2 Trial of Pharmacological Ascorbate With Concurrent Chemotherapy and Radiation Therapy for Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Non-Small Cell Lung Cancer
Nonsmall Cell Lung Cancer
Non-Small-Cell Lung Carcinoma
NSCLC
Keywords: pharmacological ascorbate
ascorbic acid
radiation
chemotherapy
carboplatin
paclitaxel
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
name: Holden Comprehensive Cancer Center
First posted: 2016-09-19
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression rate at completion of radiation and chemotherapy
timeFrame: 3 to 4 weeks after last radiation treatment
Secondary outcomes:
measure: Tumor response
timeFrame: Every six months for up to 20 years post-treatment
measure: Progression free survival (PFS)
timeFrame: Every six months for up to 20 years post-treatment
measure: Overall survival (OS)
timeFrame: Every three months for up to 20 years post-treatment
measure: Adverse event frequency and categorization
timeFrame: Weekly for the first 7 weeks, then monthly for 3 months, then every 6 months through 2 years post-treatment
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Cener
state: Iowa
Study officials:
affiliation: University of Iowa
name: Joseph J Cullen, MD, FACS
role: STUDY_DIRECTOR
References:
citation: Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Schultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR, Allen BG. O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017 Apr 10;31(4):487-500.e8. doi: 10.1016/j.ccell.2017.02.018. Epub 2017 Mar 30.