A Phase 2 Study Adding Ascorbate to Chemotherapy and Radiation Therapy for NSCLC

Study Overview
=================
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.

Official Title
-----------------
A Phase 2 Trial of Pharmacological Ascorbate With Concurrent Chemotherapy and Radiation Therapy for Non-small Cell Lung Cancer

Conditions
-----------------
Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer, Non-Small-Cell Lung Carcinoma, NSCLC

Intervention / Treatment
-----------------
* Drug: Radiation Therapy
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Ascorbic Acid


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ChemoRT + Ascorbate<br>Radiation therapy, intravenous paclitaxel, intravenous carboplatin, intravenous ascorbic acid (pharmacological ascorbate) | Drug: Radiation Therapy<br>* 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<br>* Other names: XRT;Drug: Paclitaxel<br>* 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<br>* Other names: Taxol;Drug: Carboplatin<br>* 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<br>* Other names: Paraplatin NovaPlus;Drug: Ascorbic Acid<br>* 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<br>* Other names: Pharmacological ascorbate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression rate at completion of radiation and chemotherapy | Tumor measurement from CT scan, using the RECIST criteria to define progression | 3 to 4 weeks after last radiation treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | 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. | Every six months for up to 20 years post-treatment | 
| Progression free survival (PFS) | 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 | Every six months for up to 20 years post-treatment | 
| Overall survival (OS) | Time, measured in months, from start of radiation to death from any cause. | Every three months for up to 20 years post-treatment | 
| Adverse event frequency and categorization | 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 | Weekly for the first 7 weeks, then monthly for 3 months, then every 6 months through 2 years post-treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
radiation, pharmacological ascorbate, ascorbic acid, chemotherapy, carboplatin, paclitaxel