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

16 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Gemcitabine combined with radiation therapy for pancreatic cancer?

Research shows that Gemcitabine, when combined with radiation therapy, is effective in treating localized, unresectable pancreatic cancer. Studies indicate that Gemcitabine has radiosensitizing properties, meaning it can make cancer cells more sensitive to radiation, potentially improving treatment outcomes. ^{1 2 3 4 5}

Is the combination of Gemcitabine and radiation therapy safe for humans?

Studies show that Gemcitabine combined with radiation therapy is generally safe for treating pancreatic and non-small-cell lung cancer, but the safety depends on the dose and schedule. Careful management of radiation fields and Gemcitabine doses is important to minimize side effects. ^{1 3 6 7 8}

What makes the Gemcitabine + Vitamin C + Radiation treatment unique for pancreatic cancer?

This treatment is unique because it combines Gemcitabine, a drug that makes cancer cells more sensitive to radiation, with Vitamin C and radiation therapy, potentially enhancing the effectiveness of the treatment compared to using Gemcitabine or radiation alone. ^{2 4 9 10 11}

What is the purpose of this trial?

This is a phase 1 (first in man) study testing the safety of adding high dose ascorbate (vitamin C) to standard radiation and chemotherapy for treatment of pancreatic cancer.

Research Team

Joseph J Cullen, MD, FACS

Principal Investigator

The University of Iowa Hospitals & Clinics

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Combining gemcitabine with radiation in pancreatic cancer: understanding important variables influencing the therapeutic index. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Is concomitant radiotherapy necessary with gemcitabine-based chemotherapy in pancreatic cancer? [2022]

5. England pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy and chemoradiation with gemcitabine after R1 resection in patients with pancreatic adenocarcinoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Optimizing chemoradiation in locally advanced non-small-cell lung cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Chemoradiation in NSCLC: focus on the role of gemcitabine. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[Radiochemotherapy with gemcitabine and cisplatin in pancreatic cancer -- feasible and effective]. [2022]