Vitamin C + Radiation Therapy for Pancreatic Cancer

(XACT-PANC-2 Trial)

Overseen By Joseph Caster, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph J. Cullen

Must be taking: Gemcitabine

Must not be taking: Warfarin, Flecainide, Methadone, others

Disqualifiers: G6PD deficiency, HIV, Insulin, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether high-dose vitamin C can reduce radiation therapy side effects and improve survival rates for people with pancreatic cancer. It compares standard treatment with an experimental therapy that includes vitamin C. Patients with a confirmed diagnosis of pancreatic adenocarcinoma, who are scheduled to receive gemcitabine-based chemoradiation, might be suitable for this study. The goal is to determine if vitamin C can ease cancer treatment on the body and potentially improve outcomes. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop taking my current medications for the trial?

The trial requires you to stop taking certain medications, like warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide, unless you can switch to a different drug. If you're on any of these, you'll need to discuss alternatives with your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that high-dose vitamin C, when combined with gemcitabine (a common chemotherapy drug for pancreatic cancer), is generally safe. Some studies found that patients taking 75 grams of vitamin C three times a week experienced no negative effects on their health or cancer progression.

Early findings also suggest that combining vitamin C with gemcitabine does not cause unexpected side effects. This combination has been tested in small groups, and while more research is needed, initial results are promising regarding safety.

Overall, current evidence suggests that adding high-dose vitamin C to standard chemotherapy is safe for patients with pancreatic cancer. However, as with any treatment, individual experiences may vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the investigational therapy for pancreatic cancer because it includes pharmacological ascorbate, or high-dose vitamin C, which is not a standard component in current treatment options like chemotherapy and radiation therapy alone. This therapy could potentially enhance the effectiveness of radiation by increasing the sensitivity of cancer cells to the treatment. Unlike the standard regimen of gemcitabine and radiation, the addition of vitamin C might offer a new way to target and weaken cancer cells, making them more susceptible to existing therapies. This innovative combination has the potential to improve outcomes for patients facing this challenging condition.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that high doses of vitamin C might help treat pancreatic cancer. In this trial, participants in the investigational therapy arm will receive high-dose vitamin C (ascorbate) alongside standard chemotherapy and radiation therapy. Earlier studies demonstrated that patients who received vitamin C with standard chemotherapy lived longer, and their cancer progressed more slowly. Lab tests have also found that vitamin C can slow tumor growth, suggesting it could enhance the effects of radiation and chemotherapy by more effectively targeting cancer cells. Overall, this combination might increase survival rates for patients with pancreatic cancer without causing additional harmful side effects. ^{2 3 5 6 7}

Who Is on the Research Team?

Joseph Caster, MD, PhD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for adults with pancreatic cancer who are referred for gemcitabine-based chemoradiation. They must not have other active cancers needing immediate treatment, uncontrolled illnesses, or be on certain medications like warfarin. Participants need to avoid alcohol and some supplements, have a good performance status, and agree to use birth control.

Inclusion Criteria

I am referred for treatment combining chemotherapy with radiation.

I don't have any other cancer needing immediate treatment.

Not experiencing an uncontrolled illness such as infection requiring inpatient admission, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other condition that would limit compliance with the study requirements or unacceptably increase risk to the participant (as determined by study team members).

Exclusion Criteria

I have not had any cancer treatment, including radiation, in the last 2 weeks.

I have G6PD deficiency.

I am HIV positive and on anti-retroviral therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine chemotherapy weekly and daily radiation therapy, with some receiving additional pharmacological ascorbate

6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for long-term side effects and quality of life impacts post-treatment

Up to 5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbate
• Gemcitabine
• Radiation Therapy

Trial Overview The study tests if high-dose vitamin C (ascorbate) can reduce side effects of radiation therapy in pancreatic cancer patients and possibly improve survival rates. Patients will receive ascorbate alongside standard gemcitabine chemotherapy and radiation therapy.

How Is the Trial Designed?

Group I: Investigational Therapy (ASC) Experimental Treatment 3 Interventions

75 grams of pharmacological ascorbate, daily (M-F) 600 mg/m2 of gemcitabine, once a week for up to 6 weeks 50 to 50.4 Gray of radiation therapy delivered using a volumetric arc therapy (VMAT) technique

Group II: Standard Therapy (ChemoRT) Active Control 2 Interventions

600 mg/m2 of gemcitabine, once a week for up to 6 weeks 50 to 50.4 Gray of radiation therapy delivered using a volumetric arc therapy (VMAT) technique

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Joseph J. Cullen

Lead Sponsor

Trials

5

Recruited

100+

Joseph J. Cullen, MD, FACS

Lead Sponsor

Trials

4

Recruited

110+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39369582/

A randomized trial of pharmacological ascorbate, gemcitabine ... Conclusions: P-AscH- infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213231724003537

A randomized trial of pharmacological ascorbate ... P-AscH − infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23381814/

results from a phase I clinical trial - PubMed - NIH Background: Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01515046?cond=%22Pancreas%20Disease%22&intr=%22Vitamins%22&viewType=Table&rank=10

Clinical Trial of High-dose Vitamin C for Advanced ... This is a phase II study. It is designed to provide information about if high-dose ascorbate (vitamin C) increases survival for pancreatic cancer patients.

5. nature.com nature.com/articles/s41598-017-17568-8

High Dose Parenteral Ascorbate Inhibited Pancreatic ... Ascorbate at 5 mM significantly decreased the percentage of colony formation in all tested cancer cells (Fig. 1B). Again, catalase completely ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4895694/

Treatment of Pancreatic Cancer with Pharmacological ... The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01049880

NCT01049880 | A Research Trial of High Dose Vitamin C ... This study is designed to determine the maximum tolerated dose of vitamin C when given with a standard chemotherapy for people who have metastatic pancreatic ...