High-Dose Vitamin C + Chemotherapy for Pancreatic Cancer

Overseen By Daniel J. Berg, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph J. Cullen

Must be taking: Gemcitabine, Nab-paclitaxel

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

Disqualifiers: G6PD deficiency, Insulin use, HIV therapy, 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: 2

Duration: Until disease progression (months to years)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding high-dose vitamin C (pharmacological ascorbate) to standard chemotherapy aids in treating a type of advanced pancreatic cancer. Participants will be divided into two groups: one will receive the standard cancer treatment, while the other will receive the same treatment plus vitamin C. The study aims to determine if vitamin C enhances treatment effectiveness. Individuals with metastatic pancreatic cancer who have not yet undergone chemotherapy may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if you join this trial. Specifically, if you are on warfarin, flecainide, methadone, amphetamines, quinidine, or chlorpropamide and cannot switch to another drug, you may not be eligible to participate.

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

Research has shown that high-dose vitamin C is generally safe when combined with common chemotherapy drugs like gemcitabine. In one study, patients who received this combination found the treatment manageable, with no unexpected side effects.

This suggests that adding high-dose vitamin C to chemotherapy might be safe for patients. However, as this trial remains in the early stages, more information is needed to fully confirm its safety. Prospective participants may find this information helpful in understanding what to expect regarding safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about combining high-dose vitamin C with standard chemotherapy for pancreatic cancer because it adds a potentially powerful twist to existing treatments. While gemcitabine and nab-paclitaxel are already standard care, the introduction of pharmacological ascorbate (vitamin C) is unique. Vitamin C at high doses may act as a pro-oxidant, generating reactive oxygen species that can damage cancer cells while leaving healthy cells unharmed. This new approach could enhance the effectiveness of chemotherapy, potentially improving outcomes for patients with this challenging condition.

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

Research has shown that adding high-dose vitamin C to chemotherapy may aid in treating pancreatic cancer. In this trial, participants in the Ascorbate group will receive high-dose vitamin C alongside standard chemotherapy with Gemcitabine and nab-paclitaxel. Studies have found that this combination can extend survival time without causing additional side effects. Vitamin C appears to slow tumor growth and make cancer cells more responsive to treatment. Specifically, patients with advanced pancreatic cancer experienced longer periods without disease progression when they received vitamin C with standard chemotherapy. This suggests that high-dose vitamin C could be a promising addition to current cancer treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Joseph J. Cullen, MD, FACS

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic adenocarcinoma who are recommended gemcitabine and nab-paclitaxel treatment. They must have a certain platelet count, acceptable kidney function, not be pregnant, use birth control, and cannot have had prior chemotherapy for metastatic disease or other recent treatments.

Inclusion Criteria

My initial cancer treatment didn't work or I can't have surgery or radiation to cure it.

My kidney function tests are within the required range.

Commit to using birth control during the study (all participants)

Exclusion Criteria

I have moderate to severe side effects from past treatments.

I am taking medication like warfarin or methadone and cannot change it.

Enrolled in another therapeutic clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine and nab-paclitaxel chemotherapy, with the intervention group also receiving high-dose ascorbate

Until disease progression (months to years)

Weekly visits for chemotherapy and ascorbate administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with life-long follow-up

Life-long

Every 2 months for up to 20 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• nab-paclitaxel
• Pharmacological ascorbate

Trial Overview The PACMAN 2.1 study tests high-dose vitamin C (ascorbate) added to standard chemotherapy (gemcitabine and nab-paclitaxel) in patients with advanced pancreatic cancer. Participants are randomly assigned to either the standard treatment group or the one receiving additional ascorbate.

How Is the Trial Designed?

Group I: Ascorbate group Experimental Treatment 3 Interventions

Each cycle is 4 calendar weeks Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Pharmacological ascorbate: 75 grams, three times weekly for 4 weeks

Group II: Control Active Control 2 Interventions

Each cycle is 4 calendar weeks Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Each cycle has 1 rest week

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+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

McGuff Pharmaceuticals, Inc.

Industry Sponsor

Trials

4

Recruited

130+

Published Research Related to This Trial

In a study of 11 patients with metastatic or recurrent pancreatic cancer, the combination of nab-paclitaxel and gemcitabine showed promising efficacy, with a 6-month overall survival rate of 66.7% and a disease control rate of 90.9%.

The treatment was well tolerated, with no treatment-related deaths and manageable side effects, making nab-paclitaxel plus gemcitabine a potential standard treatment for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. Takeda, Y., Katsura, Y., Ohmura, Y., et al.[2022]

A retrospective analysis of 59 patients with advanced refractory pancreatic cancer showed that the combination of nab-paclitaxel and gemcitabine (AG) is active as a second-line or beyond treatment, with 10% achieving a partial response and 47% having stable disease.

The median overall survival was 3.9 months and progression-free survival was 3 months, with toxicity levels similar to those reported in the earlier MPACT trial, indicating that AG has manageable side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. Palacio, S., Hosein, PJ., Reis, I., et al.[2020]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

The combination of nab-paclitaxel and gemcitabine is an effective first-line treatment for metastatic pancreatic cancer, significantly improving overall survival as demonstrated in the phase III trial (MPACT).

In this case study of a 64-year-old man with recurrent pancreatic cancer, the treatment was generally well-tolerated, although he experienced Grade 3 neutropenia, leading to missed doses; he ultimately passed away 9 months after starting chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A Case of Gemcitabine and Nab-Paclitaxel Therapy for Multiple Metastatic Pancreatic Cancer]. Takashima, Y., Shibamoto, J., Kawamura, Y., et al.[2022]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

In a phase 2 study involving 36 patients with advanced pancreatic cancer, the combination of cisplatin and gemcitabine showed promising activity, with 62.8% of patients achieving stable disease or better, and a median survival of 9.5 months.

While significant hematological toxicities were observed, they were mostly asymptomatic, and the treatment regimen demonstrated potential for improving survival, warranting further investigation in a larger randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of weekly cisplatin and gemcitabine in patients with advanced pancreatic cancer: is this a strategy still worth pursuing? Clayton, AJ., Mansoor, AW., Jones, ET., et al.[2022]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

Citations

1. 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.

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9547864/

Pharmacological Ascorbate Enhances Chemotherapies in ... Pharmacological ascorbate has been shown to increase tumor-specific cytotoxicity in a dose-dependent manner across multiple cancer cell lines in in vitro and in ...

4. emjreviews.com emjreviews.com/oncology/news/high-dose-vitamin-c-improves-survival-in-pancreatic-cancer/

High-Dose Vitamin C Improves Survival in Pancreatic Cancer High-dose intravenous vitamin C doubles survival in metastatic pancreatic cancer, extending life without added toxicity or reduced quality ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03541486

Study Details | NCT03541486 | A Clinical Trial Evaluating ... A Clinical Trial Evaluating the Effect of Pharmacological Ascorbate on Radiation Therapy for Pancreatic Cancer Patients (XACT-PANC-2) · Study Overview · Contacts ...

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. 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 ...