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A Phase 2 Study Adding Ascorbate to Chemotherapy and Radiation Therapy for NSCLC (XACT-LUNG)

Primary Purpose

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

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Radiation Therapy

Paclitaxel

Carboplatin

Ascorbic Acid

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring pharmacological ascorbate, ascorbic acid, radiation, chemotherapy, carboplatin, paclitaxel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Holden Comprehensive Cancer CenerRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ChemoRT + Ascorbate

Arm Description

Radiation therapy, intravenous paclitaxel, intravenous carboplatin, intravenous ascorbic acid (pharmacological ascorbate)

Outcomes

Primary Outcome Measures

Progression rate at completion of radiation and chemotherapy

Tumor measurement from CT scan, using the RECIST criteria to define progression

Secondary Outcome Measures

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.

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

Overall survival (OS)

Time, measured in months, from start of radiation to death from any cause.

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

Full Information

NCT ID

NCT02905591

First Posted

September 14, 2016

Last Updated

August 15, 2023

Sponsor

Joseph J. Cullen, MD, FACS

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI), Holden Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT02905591

Brief Title

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

Acronym

XACT-LUNG

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 16, 2018 (Actual)

Primary Completion Date

December 1, 2025 (Anticipated)

Study Completion Date

December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Joseph J. Cullen, MD, FACS

Collaborators

National Institutes of Health (NIH), National Cancer Institute (NCI), Holden Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ChemoRT + Ascorbate

Arm Type

Experimental

Arm Description

Radiation therapy, intravenous paclitaxel, intravenous carboplatin, intravenous ascorbic acid (pharmacological ascorbate)

Intervention Type

Drug

Intervention Name(s)

Radiation Therapy

Other Intervention Name(s)

external beam radiation therapy (EBRT), intensity modulated radiation therapy (IMRT), Volumetric Arc Therapy (VMAT), XRT

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

NovaPlus CARBOplatin, Amerinet Choice Carboplatin, Paraplatin, Paraplatin NovaPlus

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ascorbic Acid

Other Intervention Name(s)

Ascorbate, Vitamin C, Pharmacological ascorbate

Intervention Description

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

Primary Outcome Measure Information:

Title

Progression rate at completion of radiation and chemotherapy

Description

Tumor measurement from CT scan, using the RECIST criteria to define progression

Time Frame

3 to 4 weeks after last radiation treatment

Secondary Outcome Measure Information:

Title

Tumor response

Description

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.

Time Frame

Every six months for up to 20 years post-treatment

Title

Progression free survival (PFS)

Description

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

Time Frame

Every six months for up to 20 years post-treatment

Title

Overall survival (OS)

Description

Time, measured in months, from start of radiation to death from any cause.

Time Frame

Every three months for up to 20 years post-treatment

Title

Adverse event frequency and categorization

Description

Time Frame

Weekly for the first 7 weeks, then monthly for 3 months, then every 6 months through 2 years post-treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Bryan G Allen, MD, PhD

Phone

319-353-8836

bryan-allen@uiowa.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Muhammad Furqan, MD

Phone

319-356-1527

muhammad-furqan@uiowa.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joseph J Cullen, MD, FACS

Organizational Affiliation

University of Iowa

Official's Role

Study Director

Facility Information:

Facility Name

Holden Comprehensive Cancer Cener

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sandy Vollstedt, RN, BSN, OCN

Phone

319-353-7143

sandy-vollstedt@uiowa.edu

First Name & Middle Initial & Last Name & Degree

Heather Brown, RN, BAN, OCN

Phone

319-384-7912

heather-brown@uiowa.edu

First Name & Middle Initial & Last Name & Degree

Bryan G Allen, MD, PhD

First Name & Middle Initial & Last Name & Degree

Muhammad Furqan, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data will be shared upon request in compliance with the IRB application and protocol.

IPD Sharing Time Frame

Upon request.

IPD Sharing Access Criteria

Contact the investigator or sub-investigator to initiate a request. A contract may be required between institutions. Data will be shared only from those participants who consented to sharing.

Citations:

PubMed Identifier

28366679

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. Erratum In: Cancer Cell. 2017 Aug 14;32(2):268.

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

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