Gemcitabine + Vitamin C + Radiation for Pancreatic Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joseph J. Cullen

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

Disqualifiers: G6PD deficiency, Second malignancy, HIV, others

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

Compensation: Varies

Number of Visits: 3

Duration: 5-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding high doses of vitamin C to standard chemotherapy and radiation is safe for treating pancreatic cancer. The study will test various doses of vitamin C alongside the usual treatment to determine patient tolerance. Individuals with pancreatic cancer, diagnosed through a biopsy and able to handle a small test dose of vitamin C, might be suitable candidates for this trial. The primary goal is to assess the safety of this new treatment approach. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as insulin and specific drugs like flecainide, methadone, amphetamines, quinidine, and chlorpropamide, unless a substitution can be made. If you are on these medications, you may 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 adding vitamin C to gemcitabine, a common chemotherapy drug, is generally safe for people with pancreatic cancer. Studies have found that high doses of vitamin C, when combined with gemcitabine, do not increase side effects compared to gemcitabine alone. This combination has been used in patients with advanced pancreatic cancer without causing additional harmful effects.

In some cases, high-dose vitamin C has demonstrated potential benefits, such as targeting cancer cells while sparing healthy cells. It works in several ways, including boosting the immune system and directly attacking cancer cells.

The current trial is in its early phase, focusing mainly on safety. Researchers are closely monitoring how well participants tolerate the treatment. The trial begins with 50 grams of vitamin C and gradually increases the dose to determine the optimal amount with the fewest side effects. If a dose is well-tolerated, higher doses are tested.

Overall, evidence suggests that combining vitamin C with gemcitabine is safe for most patients, but ongoing monitoring in trials ensures patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for pancreatic cancer because it combines high-dose vitamin C (ascorbate) with the chemotherapy drug gemcitabine and radiation therapy, offering a potentially novel approach. Unlike standard treatments that primarily rely on chemotherapy and radiation, the addition of vitamin C in high doses may enhance the cancer-killing effects of radiation and chemotherapy by generating oxidative stress in cancer cells. This combination approach might improve treatment effectiveness and overcome resistance seen in conventional therapies. Additionally, delivering vitamin C intravenously allows for much higher concentrations in the body, which could be crucial in targeting cancer cells more effectively.

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

Research has shown that adding high-dose vitamin C to regular chemotherapy and radiation may help pancreatic cancer patients live longer. In this trial, participants will receive varying doses of vitamin C (ascorbate) alongside gemcitabine and radiation therapy. One study found that patients who received both chemotherapy and vitamin C lived, on average, 16 months, while those who did not receive the vitamin lived only 8 months. Another study demonstrated that using vitamin C with gemcitabine in mice slowed tumor growth more effectively than gemcitabine alone. These findings suggest that this treatment approach might enhance the effectiveness of existing therapies for pancreatic cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Joseph J Cullen, MD, FACS

Principal Investigator

The University of Iowa Hospitals & Clinics

Are You a Good Fit for This Trial?

This trial is for adults over 18 with pancreatic adenocarcinoma, who can tolerate a test dose of vitamin C and have normal liver function, blood clotting, kidney function, and white blood cell count. They must not be pregnant or on certain drugs like insulin or methadone that can't be replaced.

Inclusion Criteria

Not pregnant

I can take care of myself but might not be able to do heavy physical work.

You have at least 100,000 platelets per cubic millimeter of blood.

Exclusion Criteria

I have G6PD deficiency.

Pregnant or lactating women: The risks of radiation and chemotherapy to a fetus are well documented

I am HIV-positive and understand high-dose vitamin C may affect my HIV medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high doses of intravenous ascorbate during daily radiation therapy treatments, along with weekly gemcitabine

5-6 weeks

Daily visits (Monday through Friday)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with adverse events assessed monthly

2 years

Every 3 months

Long-term follow-up

Participants are monitored for disease progression and overall survival

Up to 10 years

Monthly

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbate
• Gemcitabine
• Radiation therapy

Trial Overview

The study tests the safety of high-dose vitamin C combined with standard chemotherapy (Gemcitabine) and radiation therapy in treating pancreatic cancer. It's an early-stage trial to see if this mix is safe for patients.

How Is the Trial Designed?

Group I: 75g Ascorbate Experimental Treatment 3 Interventions

If the 50g arm is tolerated, the study opens the 75g arm. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 75 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

Group II: 50g Ascorbate Experimental Treatment 3 Interventions

This arm is the initial starting dose. The first study participant will be assigned the 50g ascorbate arm. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 50 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

Group III: 25g Ascorbate Experimental Treatment 3 Interventions

This study arm will only be used if participants cannot tolerate the 50g arm. If participants cannot tolerate 50 grams of Ascorbate, the 25g arm is opened. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 25 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

Group IV: 100g Ascorbate Experimental Treatment 3 Interventions

If the 75g arm is tolerated, the study opens the 100g arm. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 100 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

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+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

Published Research Related to This Trial

In a Phase II study involving 28 patients with unresectable locally advanced pancreatic cancer, the combination of weekly Gemcitabine and external beam radiotherapy was found to be safe, with 86% of patients completing the treatment despite some experiencing significant toxicities.

The treatment resulted in a median survival time of 10.3 months, with 21% of patients showing a partial response and 57% maintaining stable disease, indicating potential efficacy in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group study. Cardenes, HR., Moore, AM., Johnson, CS., et al.[2022]

In a systematic review of four studies involving 336 participants, combining gemcitabine with radiotherapy did not improve overall survival or progression-free survival compared to gemcitabine alone.

However, the addition of radiotherapy led to a higher incidence of severe side effects, such as anemia and fatigue, indicating that this combination may not be safe or beneficial for patients with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is concomitant radiotherapy necessary with gemcitabine-based chemotherapy in pancreatic cancer? Zhang, X., Huang, HJ., Feng, D., et al.[2022]

The study involved 22 patients with Stage II and III pancreatic adenocarcinoma, and the treatment regimen of gemcitabine followed by concurrent gemcitabine and radiation was well tolerated, with no toxic deaths reported and manageable side effects.

After a median follow-up of 15 months, the median overall survival was 15 months, indicating that this treatment approach is feasible and may provide a foundation for further investigation into its effectiveness in improving outcomes for pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study. Van Laethem, JL., Demols, A., Gay, F., et al.[2022]

In a study of 41 patients with nonmetastatic pancreatic cancer, full-dose gemcitabine combined with radiation therapy was found to be well tolerated, with manageable side effects such as grade 3 neutropenia, nausea, and vomiting.

The treatment led to a significant reduction in CA 19-9 levels and a one-year survival rate of 73%, suggesting that this regimen could be effective and warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial. Small, W., Berlin, J., Freedman, GM., et al.[2022]

Gemcitabine has shown good tolerance and effectiveness in treating non-small-cell lung cancer, achieving response rates of 30% to 60% when used in combination with radiation therapy.

In a phase III trial involving 187 patients with unresectable stage III non-small-cell lung cancer, the combination of gemcitabine and cisplatin as induction therapy led to a median survival of 18 months and a median progression-free survival of 10 months, demonstrating its efficacy without compromising the safety of concurrent radiation treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing chemoradiation in locally advanced non-small-cell lung cancer. Curran, WJ., Choy, H.[2022]

Citations

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The average overall survival (OS) at 5 years is currently 12 %, with an abysmal 3 % for those diagnosed with distant disease [5]. Despite ...

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Gemcitabine–ascorbate combinations administered to mice bearing pancreatic tumor xenografts consistently enhanced inhibition of growth compared to gemcitabine ...

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These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients.

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The use of pharmacological ascorbate in combination with gemcitabine in patients with metastatic or unresectable pancreatic adenocarcinoma should be safe and ...