FOLFIRINOX + 9-ING-41 for Pancreatic Cancer

Recruiting at3 trial locations

Overseen by Colin Weekes, M.D., Ph.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Colin D. Weekes, M.D., PhD

Must not be taking: Cimetidine, Strong CYP inhibitors

Disqualifiers: Prior chemotherapy, BRCA mutation, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out if an experimental drug will prevent metastatic pancreatic adenocarcinoma from becoming resistant to standard treatment for the disease. The names of the study drugs involved in this study are: * 9-ING-41 * Losartan * Ferumoxytol * FOLFIRINOX (made up of 4 different drugs): * 5-Fluorouracil (5-FU) * Oxaliplatin * Irinotecan * Leucovorin

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but if you are on an angiotensin receptor blocker (ARB) for high blood pressure and are not assigned to the losartan group, you will need to switch to a different type of blood pressure medication. Also, you cannot take cimetidine and certain other medications that affect liver enzymes.

What data supports the effectiveness of the treatment FOLFIRINOX + 9-ING-41 for pancreatic cancer?

FOLFIRINOX has been shown to improve survival and response rates in patients with metastatic pancreatic cancer compared to older treatments like gemcitabine. It is also used in various settings, including as a first-line treatment and in modified forms to improve safety and tolerability. ^{1 2 3 4 5}

Is FOLFIRINOX safe for humans?

FOLFIRINOX, used for advanced pancreatic cancer, often causes side effects that require reducing the dose, but it is generally considered safe with careful monitoring. ^{1 3 6 7 8}

How is the drug FOLFIRINOX + 9-ING-41 unique for treating pancreatic cancer?

FOLFIRINOX is a combination of four drugs (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) that is typically used for patients with advanced pancreatic cancer who are in good health. It is different from other treatments like gemcitabine because it combines multiple drugs to target cancer cells more aggressively, although it may have more side effects. ^{1 9 10 11 12}

Research Team

Colin Weekes, M.D., Ph.D.

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed metastatic pancreatic adenocarcinoma who haven't had treatment for it yet. They must have a certain level of physical fitness and adequate organ function. People with HIV, HBV, or cured HCV can join. Those with controlled brain metastases may be eligible. Pregnant women can't participate unless they use contraception.

Inclusion Criteria

My organs and bone marrow are functioning well.

I have another cancer, but it won't affect this trial's treatment.

I had hepatitis C but have been treated and cured.

Exclusion Criteria

I am not on strong medication that affects liver enzymes CYP2C19, CYP3A4, and CYP1A2.

I have a known UGT1A1 gene variation.

My pancreatic cancer is linked to a harmful BRCA gene mutation.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Establish the side effects from the study treatment to its safety before beginning the main part of the study

2-4 weeks

1-2 cycles of treatment

Complete Therapy

Participants receive FOLFIRINOX, 9-ING-41, and Losartan for up to 12 cycles

24 weeks

Bi-weekly visits for each cycle

Maintenance Therapy

Participants continue with FOLFIRINOX and other drugs until disease progression

Up to 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• 9-ING-41 (Other)
• FOLFIRINOX (Other)
• Losartan (Other)

Trial Overview The study tests if the experimental drug 9-ING-41 combined with FOLFIRINOX (a mix of four chemotherapy drugs) and Losartan prevents resistance to standard pancreatic cancer treatment in patients without prior therapy.

Participant Groups

Group I: Safety Run-In: FOLFIRINOX + 9-ING-41 + Losartan Experimental Treatment 3 Interventions

The study will begin with a Safety Run-In phase to establish the side effects from the study treatment to its safety before beginning the main part of the study, six (6) participants will receive 1-2 cycles of: * FOLFIRINOX * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle * Irinotecan portion of FOLFIRINOX on Day 1 of each 14 day study cycle * Oxaliplatin portion of FOLFIRINOX on Day 1 of each 14 day study cycle * Leucovorin portion of FOLFIRINOX on Day 1 of each 14 day study cycle * 9-ING-41 on days on days 1, 3, 8, and 11 of every 14-day cycle * Losartan daily of every 14-day cycle.

Group II: FOLFIRNINOX Experimental Treatment 1 Intervention

The study will be conducted in three parts depending on participant disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2. For initial complete therapy, participants will receive FOLFIRINOX as follows: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle up to 12 cycles (24 weeks) * Irinotecan portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * Oxaliplatin portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * Leucovorin portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) For Maintenance therapy, participants will receive FOLFIRINOX as follows: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle until disease progression For Complete Therapy Round 2, participants will repeat initial complete therapy of FOLFIRINOX until further disease progression

Group III: FOLFIRINOX + Losartan Experimental Treatment 2 Interventions

The study will be conducted in three parts depending on participant disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2. For initial complete therapy: * FOLFIRINOX * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle up to 12 cycles (24 weeks) * Irinotecan portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * Oxaliplatin portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * Leucovorin portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * Losartan daily up to 12 cycles (24 weeks) For Maintenance therapy: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle until disease progression * Losartan daily until disease progression For Complete Therapy Round 2, participants will repeat initial complete therapy of FOLFIRINOX + Losartan until further disease progression

Group IV: FOLFIRINOX + 9-ING-41 + Losartan Experimental Treatment 3 Interventions

The study conducted in 3 parts depending on disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2. For initial complete therapy: * FOLFIRINOX * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle * Irinotecan portion of FOLFIRINOX on Day 1 of each 14 day study cycle * Oxaliplatin portion of FOLFIRINOX on Day 1 of each 14 day study cycle * Leucovorin portion of FOLFIRINOX on Day 1 of each 14 day study cycle * 9-ING-41 on days 1, 3, 8, and 11 of every 14-day cycle * Losartan daily For Maintenance therapy: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle until disease progression * 9-ING-41 on days 1, 3, 8, and 11 of every 14-day cycle until disease progression * Losartan daily until disease progression For Complete Therapy Round 2, participants will repeat initial complete therapy of FOLFIRINOX + 9-ING-41+ Losartan until further disease progression

Group V: FOLFIRINOX + 9-ING-41 Experimental Treatment 2 Interventions

The study conducted in 3 parts depending on disease progression: Complete Therapy, Maintenance Therapy and Complete Therapy Round 2. For initial complete therapy: * FOLFIRINOX * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle up to 12 cycles (24 weeks) * Irinotecan portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * Oxaliplatin portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * Leucovorin portion of FOLFIRINOX on Day 1 of each 14 day study cycle up to 12 cycles (24 weeks) * 9-ING-41 on days 1, 3, 8, and 11 of every 14-day cycle up to 12 cycles (24 weeks) For Maintenance therapy: * 5Fluorouracil portion of FOLFIRINOX on Days 1-3 of each 14 day study cycle until disease progression * 9-ING-41 on days 1, 3, 8, and 11 of every 14-day cycle until disease progression For Complete Therapy Round 2, repeat of initial complete therapy until further disease progression

Who Is Running the Clinical Trial?

Colin D. Weekes, M.D., PhD

Lead Sponsor

Trials

2

Recruited

70+

Colin D. Weekes, M.D.

Lead Sponsor

Trials

2

Recruited

70+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

Actuate Therapeutics Inc.

Industry Sponsor

Trials

10

Recruited

580+

Findings from Research

In a study of 289 patients with advanced pancreatic ductal adenocarcinoma, the FOLFOXIRI chemotherapy regimen showed similar overall survival (11.1 months) compared to the standard FOLFIRINOX regimen (11.6 months), indicating no significant therapeutic advantage for FOLFOXIRI.

FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events (28.7% vs. 19.5% for FOLFIRINOX), suggesting that while it is feasible, it may lead to more severe side effects without improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. Vienot, A., Chevalier, H., Bolognini, C., et al.[2020]

FOLFIRINOX, a combination chemotherapy regimen, has been shown to significantly improve overall survival and progression-free survival in patients with metastatic pancreatic cancer compared to the traditional treatment with gemcitabine, based on results from the PRODIGE 4/ACCORD 11 trial.

While FOLFIRINOX is associated with higher toxicity rates, including febrile neutropenia and diarrhea, its rapid adoption in clinical practice highlights its effectiveness, and further studies are needed to explore its benefits in other treatment settings like second-line therapy and adjuvant chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. Lambert, A., Gavoille, C., Conroy, T.[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]

In a phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., et al.[2020]

In a study of 243 patients with advanced pancreatic adenocarcinoma treated with FOLFIRINOX, the relative dose intensity (RDI) of the treatment agents did not significantly correlate with disease control or objective response, suggesting that dose reductions may not compromise treatment effectiveness.

The median cumulative multi-drug RDI was 80%, and including RDI in predictive models did not enhance the ability to forecast disease control, indicating that oncologists can safely adjust doses without fearing a loss of therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. Vary, A., Lebellec, L., Di Fiore, F., et al.[2022]

In a multicenter phase II study involving 31 patients with locally advanced pancreatic cancer (LAPC) and 44 with metastatic pancreatic cancer (MPC), modified FOLFIRINOX showed comparable efficacy to full-dose FOLFIRINOX in MPC, with a response rate of 35.1% and a median overall survival of 10.2 months.

The study found that modified FOLFIRINOX significantly reduced adverse events such as neutropenia, vomiting, and fatigue, while demonstrating notable efficacy in LAPC with a median progression-free survival of 17.8 months and overall survival of 26.6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Stein, SM., James, ES., Deng, Y., 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]

A nomogram was developed to predict 6-month survival in patients with metastatic and locally advanced pancreatic cancer treated with FOLFIRINOX, based on four key prognostic factors: performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio.

The nomogram demonstrated good accuracy in predicting outcomes, with a C index of 0.762 in an independent validation cohort, helping to identify patient subsets with varying prognoses based on the number of poor prognostic features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan. Fornaro, L., Leone, F., Vienot, A., et al.[2020]

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 342 patients with metastatic pancreatic cancer, the FOLFIRINOX chemotherapy regimen significantly improved overall survival (11.1 months) compared to gemcitabine (6.8 months), indicating it is a more effective first-line treatment option.

While FOLFIRINOX showed a higher objective response rate (31.6% vs. 9.4% for gemcitabine), it also resulted in more adverse events, including a 5.4% incidence of febrile neutropenia, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. Conroy, T., Desseigne, F., Ychou, M., et al.[2023]

In a study of 18 patients with locally advanced pancreatic cancer (LAPC), neoadjuvant therapy using FOLFIRINOX resulted in a promising R0 resection rate of 44%, indicating that a significant portion of patients became eligible for surgical removal of their tumors after treatment.

The treatment showed high efficacy with a 1-year overall survival rate of 100% and a progression-free survival rate of 83%, although it was associated with notable chemotherapy-related toxicities, including neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. Hosein, PJ., Macintyre, J., Kawamura, C., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. China pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. [2020]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. [2022]

8. China pubmed.ncbi.nlm.nih.gov

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

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

Validated Nomogram Predicting 6-Month Survival in Pancreatic Cancer Patients Receiving First-Line 5-Fluorouracil, Oxaliplatin, and Irinotecan. [2020]

10. 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]

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

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. [2023]

12. England pubmed.ncbi.nlm.nih.gov

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. [2022]