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

Trial Summary

What is the purpose of this trial?

This will be a phase I/II trial examining the safety and tolerability of pre-operative mFOLFIRINOX in combination with peri-operative oral hydroxychloroquine (FHQ) in the treatment of subjects with adenocarcinoma of the pancreas. Subjects will be staged prior to protocol entry by contrast-enhanced helical abdominal CT scan done using a pancreas mass protocol or EUS. Eligible subjects with biopsy-proven, resectable pancreatic adenocarcinoma without evidence of venous or arterial involvement on CT scan receive HCQ orally in combination with mFOLFIRINOX prior to surgery. Hydroxychloroquine will begin with the first dose of mFOLFIRINOX and continue for 2 weeks post-operatively. Three to six weeks after the last dose of mFOLFIRINOX, patients will undergo surgical exploration and pancreatectomy if technically feasible and all toxicities have resolved. Pathologic specimens will undergo detailed histopathologic and immunohistochemical evaluations with particular attention to the six surgical margins of resection: the bile duct margin (for Whipple specimens), the margin of pancreatic transection, the retroperitoneal margin, the proximal and distal duodenal margins (for Whipple specimens), and the portal vein margin along the pancreatic head (for Whipple specimens) or medial pancreas (for distal pancreatectomies). Tissue specimens will be stored at -80C for future correlative studies of autophagy and tumor response to protocol therapy. Ten to fourteen weeks following completion of successful surgical removal of their tumor, subjects will undergo repeat staging studies per standard of care. Subjects will pursue standard of care adjuvant therapy options at the discretion of their physician.

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.

What data supports the effectiveness of the drug mFOLFIRINOX + Hydroxychloroquine for pancreatic cancer?

Research shows that modified FOLFIRINOX (mFOLFIRINOX) can be effective for treating pancreatic cancer, especially when used as a second-line treatment or in a modified form to improve safety and tolerability. However, the specific combination with Hydroxychloroquine for pancreatic cancer has not been directly studied in the provided research. ^{1 2 3 4 5}

Is mFOLFIRINOX safe for treating pancreatic cancer?

Modified FOLFIRINOX (mFOLFIRINOX) has been studied for safety in treating pancreatic cancer, and while it is generally considered effective, it can have significant side effects. These side effects are often less severe than those of the standard FOLFIRINOX regimen, but they still require careful management. ^{2 3 6 7 8}

How is the drug mFOLFIRINOX + Hydroxychloroquine unique for treating pancreatic cancer?

The treatment mFOLFIRINOX is a modified version of the original FOLFIRINOX regimen, designed to be less toxic by using a reduced dosage, making it potentially safer for patients with pancreatic cancer. Adding Hydroxychloroquine, which is not typically part of standard pancreatic cancer treatments, may offer a novel approach by potentially enhancing the effectiveness of mFOLFIRINOX. ^{1 2 3 9 10}

Research Team

Brian Boone, MD

Principal Investigator

WVU Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. England 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). [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. [2018]

3. China 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. [2023]

5. United States 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. [2023]

6. China 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. [2023]

7. United States 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. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. [2019]

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

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study. [2023]