mFOLFIRINOX + Hydroxychloroquine for Pancreatic Cancer

Overseen By Brian Boone

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: West Virginia University

Must be taking: mFOLFIRINOX, Hydroxychloroquine

Must not be taking: Anti-epileptics

Disqualifiers: Metastasis, HIV, Porphyria, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for pancreatic cancer, focusing on their safety and tolerability. It combines a chemotherapy regimen called mFOLFIRINOX with hydroxychloroquine, a medication typically used for malaria, to determine its effectiveness for patients whose cancer can be surgically removed. Individuals with confirmed pancreatic adenocarcinoma that hasn't spread to major blood vessels and who haven't recently undergone chemotherapy might be suitable candidates for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on enzyme-inducing anti-epileptic medications like phenytoin or carbamazepine, you cannot participate in the trial.

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

Research has shown that hydroxychloroquine can slow the spread of pancreatic cancer that has metastasized. Some studies have found that this may lead to longer survival times. Hydroxychloroquine targets cancer cells, potentially helping to destroy them.

Hydroxychloroquine is usually well-tolerated, but like any medication, it can cause side effects. Common side effects include an upset stomach or mild headaches. Monitoring for any negative reactions during treatment is important.

The mFOLFIRINOX treatment in this trial combines chemotherapy drugs. It has been used in other cancer treatments and is known for its potency, which may cause more noticeable side effects such as tiredness, nausea, or low blood counts.

Both hydroxychloroquine and mFOLFIRINOX have been studied previously. While they can cause side effects, these are generally manageable. Discuss any concerns with the trial team to ensure the best care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of mFOLFIRINOX and hydroxychloroquine for pancreatic cancer because it offers a unique approach compared to current treatments. While traditional therapies like chemotherapy target cancer cells directly, hydroxychloroquine works differently by disrupting the cancer cells' ability to protect themselves through a process called autophagy. This combination aims to enhance the effectiveness of mFOLFIRINOX, potentially leading to better outcomes for patients. By targeting cancer cells in a new way, this treatment could provide a more powerful option for combating pancreatic cancer.

What evidence suggests that mFOLFIRINOX + Hydroxychloroquine might be an effective treatment for pancreatic cancer?

Research has shown that hydroxychloroquine, which participants in this trial may receive, can slow the growth of pancreatic cancer cells by blocking pathways essential for cancer cell survival. Studies have found that, when combined with other treatments, hydroxychloroquine can enhance the effectiveness of chemotherapy. Specifically, it can alter the tumor environment, facilitating chemotherapy's action. Additionally, past studies demonstrated that hydroxychloroquine can increase survival by reducing cancer spread. Overall, these findings suggest that hydroxychloroquine may improve treatments for pancreatic cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Brian Boone, MD

Principal Investigator

WVU Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with resectable pancreatic adenocarcinoma, confirmed by biopsy and CT scan without vein or artery involvement. Participants must have normal kidney, liver, and blood function; no severe allergies to study drugs; not be on certain anti-epileptic medications; and have no history of macular degeneration or diabetic retinopathy. Pregnant women are excluded, as well as those with HIV, porphyria, uncontrolled psoriasis, recent chemotherapy within the last year or other concurrent experimental therapies.

Inclusion Criteria

I have been diagnosed with pancreatic adenocarcinoma.

I have no active cancer except possibly skin cancer.

Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

Inability to adhere to study and/or follow-up procedures

My scans show cancer near major blood vessels in my liver, making surgery difficult.

My psoriasis is under control and monitored by a specialist.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mFOLFIRINOX in combination with oral hydroxychloroquine for 4 cycles, each cycle lasting 14 days

8 weeks

Regular visits for each cycle

Surgery

Surgical exploration and pancreatectomy are performed if feasible, 3 to 6 weeks after the last dose of mFOLFIRINOX

3-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after surgery, with surveillance scans 10 to 14 weeks post-surgery

10-14 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hydroxychloroquine
• mFOLFIRINOX

Trial Overview The trial tests the safety of combining mFOLFIRINOX (a chemotherapy mix) with oral hydroxychloroquine before surgery in patients with pancreatic cancer. The treatment aims to improve surgical outcomes and will be followed by standard care adjuvant therapy post-surgery. Patients' tissue samples will also be studied for future research on autophagy's role in tumor response.

How Is the Trial Designed?

Group I: Hydroxychloroquine Experimental Treatment 1 Intervention

Hydroxychloroquine sulfate

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

Approved in European Union as mFOLFIRINOX for:

• Pancreatic ductal adenocarcinoma (PDAC)

Approved in United States as mFOLFIRINOX for:

• Advanced pancreatic cancer

Approved in Canada as mFOLFIRINOX for:

• Resectable pancreatic ductal adenocarcinoma

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Published Research Related to This Trial

In a study of 318 patients with metastatic pancreatic cancer, the modified FOLFIRINOX (mFFX) regimen showed similar overall survival and progression-free survival compared to the original FOLFIRINOX (oFFX) regimen, indicating that mFFX is just as effective.

mFFX was associated with significantly fewer adverse events, such as thrombopenia and liver dysfunction, making it a safer option for patients compared to oFFX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study. Nakazawa, J., Tsuruta, N., Shimokawa, M., et al.[2023]

In a phase III trial involving 80 patients with metastatic pancreatic adenocarcinoma, modified FOLFIRINOX (mFOLFIRINOX) significantly improved overall survival compared to S-1, with median survival rates of 9.2 months versus 4.9 months, respectively.

While mFOLFIRINOX showed higher efficacy with better response and disease control rates, it also resulted in more severe adverse events, with 56% of patients experiencing grade 3-4 side effects compared to 17% in the S-1 group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX versus S-1 as second-line chemotherapy in gemcitabine-failed metastatic pancreatic cancer patients: A randomised controlled trial (MPACA-3). Go, SI., Lee, SC., Bae, WK., et al.[2022]

In a study of 74 patients with unresectable pancreatic cancer, modified FOLFIRINOX (mFOLFIRINOX) showed a tendency for improved overall survival (10.6 months) compared to sequential chemotherapy (8.5 months), although the difference was not statistically significant.

However, mFOLFIRINOX was associated with a higher incidence of severe adverse events (grade ≥3), such as neutropenia (40.9% vs. 3.3% in sequential chemotherapy), suggesting that sequential chemotherapy may offer a better risk-benefit balance for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX versus sequential chemotherapy (FOLFIRI/FOLFOX) as a second-line treatment regimen for unresectable pancreatic cancer: A real-world analysis. Tezuka, S., Ueno, M., Oishi, R., et al.[2023]

In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), indicating it may be more effective as a second-line treatment after gemcitabine plus nab-paclitaxel.

Both S-IROX and mFFX had similar overall survival rates (14.2 months for S-IROX and 11.5 months for mFFX) and tolerability, with no significant differences in severe side effects, suggesting both regimens are viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Saito, K., Nakai, Y., Takahara, N., et al.[2022]

Modified-FOLFIRINOX (mFOLFIRINOX) significantly improves safety and tolerability for Chinese patients with locally advanced pancreatic cancer (LAPC), with a response rate of 37.1% and common severe side effects including neutropenia and anemia.

Patients with LAPC who received neoadjuvant therapy with mFOLFIRINOX and subsequently underwent surgery had a median overall survival of 27.7 months, which is significantly better than the 8.9 months seen in patients who had upfront surgery without prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Li, X., Guo, C., Li, Q., et al.[2023]

Modified-dose FOLFIRINOX (mFOLFIRINOX) demonstrated comparable efficacy to standard-dose FOLFIRINOX (sFOLFIRINOX) in treating pancreatic cancer, with similar objective response rates and overall survival outcomes among 130 patients studied.

mFOLFIRINOX was associated with significantly lower rates of severe adverse events, such as neutropenia, anorexia, and diarrhea, suggesting it is a safer option for patients who may be concerned about toxicity while maintaining effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. Kang, H., Jo, JH., Lee, HS., et al.[2022]

Neoadjuvant FOLFIRINOX treatment in patients with borderline resectable pancreatic cancer (BRPC) resulted in a median overall survival of 22.2 months and a high resection rate of 67.8%, indicating its potential effectiveness in this patient group.

The treatment was associated with manageable adverse events, with the most common being neutropenia, diarrhea, and fatigue, but no deaths were reported due to FOLFIRINOX, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. Janssen, QP., Buettner, S., Suker, M., et al.[2021]

In a study of 69 chemotherapy-naïve patients with metastatic pancreatic cancer, the modified FOLFIRINOX regimen resulted in a median overall survival of 11.2 months and a response rate of 37.7%, indicating its efficacy in this patient population.

The modified regimen demonstrated a better safety profile compared to previous studies, with a 47.8% incidence of grade 3 or higher neutropenia and fewer serious adverse events, suggesting it can be administered without prophylactic pegfilgrastim.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. Ozaka, M., Ishii, H., Sato, T., et al.[2019]

Modified FOLFIRINOX shows similar effectiveness in treating metastatic pancreatic adenocarcinoma (MPA) compared to standard FOLFIRINOX, with no significant differences in overall survival or progression-free survival among patients.

While modified FOLFIRINOX had a lower dose reduction rate, it was associated with a slightly higher incidence of severe toxicity, indicating that patient selection may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma. de Jesus, VHF., Camandaroba, MPG., Donadio, MDS., et al.[2023]

The modified FOLFIRINOX (mFOLFIRINOX) regimen demonstrated a high treatment efficacy in patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC), achieving a response rate of 55.2% among 29 evaluable patients.

The treatment was well-tolerated, with only 9 patients experiencing grade 3 or 4 adverse effects, and no patients discontinued treatment due to side effects, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. Bai, X., Su, R., Ma, T., et al.[2018]

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