ABTL0812 + FOLFIRINOX for Pancreatic Cancer

(PanC-ASAP Trial)

Recruiting at 23 trial locations

Overseen By Marc Cortal

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ability Pharmaceuticals SL

Must not be taking: PI3K/Akt/mTOR inhibitors

Disqualifiers: Non-carcinoma histology, Chronic diarrhea, Pregnancy, Recent myocardial infarction, others

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

Compensation: Varies

Number of Visits: Unknown

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, ABTL0812, combined with usual chemotherapy for patients with advanced pancreatic cancer. The goal is to see if ABTL0812 can make the chemotherapy more effective. The study includes two stages: an initial stage to find the best amount and a second stage to compare the new combination against usual care.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug FOLFIRINOX for pancreatic cancer?

FOLFIRINOX has been shown to improve survival and quality of life in patients with metastatic pancreatic cancer compared to gemcitabine, according to the PRODIGE 4/ACCORD 11 study. It is a standard first-line treatment for advanced pancreatic cancer, despite concerns about its side effects. ^{1 2 3 4 5}

What safety data exists for FOLFIRINOX in humans?

FOLFIRINOX has been used since 2010 for treating pancreatic cancer, and while it can cause side effects that sometimes require reducing the dose, it has been widely adopted in clinical practice. Studies have focused on managing these side effects and adjusting treatment to improve safety. ^{1 2 6 7 8}

What makes the ABTL0812 + FOLFIRINOX treatment unique for pancreatic cancer?

The combination of ABTL0812 with FOLFIRINOX is unique because it adds a novel drug, ABTL0812, to the standard FOLFIRINOX regimen, which is already known for its effectiveness in improving survival and quality of life in pancreatic cancer patients. This combination aims to enhance the treatment's efficacy by potentially introducing a new mechanism of action alongside the established benefits of FOLFIRINOX. ^{1 2 9 10 11}

Research Team

Marc Cortal

Principal Investigator

Ability Pharmaceuticals SL

Eligibility Criteria

Adults with confirmed metastatic pancreatic cancer, good blood counts and organ function, who haven't been treated with PI3K/Akt/mTOR pathway inhibitors. They must not have other serious medical conditions or a history of certain heart diseases. Participants need to use effective contraception and be able to follow the study protocol.

Inclusion Criteria

I have at least one tumor that can be measured and tracked for treatment response.

Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2

Total bilirubin ≤ 1.5 x ULN, Albumin ≥ 3.3 g/dL

Exclusion Criteria

I have had a heart attack in the last 6 months or have serious heart issues.

I have been treated with a PI3K/Akt/mTOR pathway inhibitor.

I am able to make my own health decisions and am not under legal supervision.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Open label phase to determine the RP2D of ABTL0812 in combination with FOLFIRINOX with dose de-escalation

5 weeks

Weekly visits for dose adjustment and monitoring

Phase II Treatment

Double blind, randomized, placebo-controlled study to evaluate ABTL0812 in combination with FOLFIRINOX

Until disease progression or unacceptable toxicities

Bi-weekly visits for chemotherapy cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Quarterly visits for monitoring

Treatment Details

Interventions

• ABTL0812
• Folfirinox
• Placebo

Trial Overview The trial is testing ABTL0812 in combination with FOLFIRINOX chemotherapy as a first-line treatment for metastatic pancreatic cancer. It's an open-label Phase I followed by a randomized Phase II study comparing this combination against placebo plus FOLFIRINOX.

Participant Groups

Group I: Arm B) PLACEBO + FOLFIRINOX Experimental Treatment 2 Interventions

FOLFIRINOX will be dosed according to the standard following regimen: * oxaliplatin 85 mg/m2, administered as 2-hour iv infusion * leucovorin 400 mg/m2, administered as 2-hour iv infusion * irinotecan 180 mg/m2, administered as 1.5-hour iv infusion * fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities. Placebo will be administered at the same volume than ABTL0812 in arm A) FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued.

Group II: Arm A) ABTL0812 + FOLFIRINOX Experimental Treatment 2 Interventions

FOLFIRINOX will be dosed according to the standard following regimen: * oxaliplatin 85 mg/m2, administered as 2-hour iv infusion * leucovorin 400 mg/m2, administered as 2-hour iv infusion * irinotecan 180 mg/m2, administered as 1.5-hour iv infusion * fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities. ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.

Who Is Running the Clinical Trial?

Ability Pharmaceuticals SL

Lead Sponsor

Trials

4

Recruited

340+

Findings from Research

FOLFIRINOX (FFX) has been shown to significantly improve median overall survival, progression-free survival, and objective response rates in patients with metastatic pancreatic cancer compared to gemcitabine, as established in the PRODIGE 4/ACCORD 11 study.

Despite initial concerns about its toxicity, FFX has been widely adopted in clinical practice, leading to new research opportunities and discussions about managing its side effects and optimizing treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic cancer and FOLFIRINOX: a new era and new questions. Marsh, Rde W., Talamonti, MS., Katz, MH., et al.[2023]

In a study of 71 patients with advanced pancreatic cancer who progressed after initial treatment with modified FOLFIRINOX, second-line chemotherapy resulted in a 7.1% partial response rate and a 27.1% disease stabilization rate.

The median overall survival for these patients was 6.2 months, with CA19.9 levels above the normal limit indicating worse survival outcomes, suggesting that certain prognostic factors can help identify patients who may benefit more from salvage chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. Caparello, C., Vivaldi, C., Fornaro, L., 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]

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 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]

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 modified FOLFIRINOX (mFOLFIRINOX) for advanced gastrointestinal cancers, including pancreatic and biliary tract cancers, the tolerability based on UGT1A1 genotype-guided dosing was not established, as dose-limiting toxicities (DLTs) exceeded acceptable limits in some patient groups.

Despite the toxicity concerns, the mFOLFIRINOX regimen showed promising efficacy, with response rates of 38% in pancreatic cancer and 21% in biliary tract cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A UGT1A1 genotype-guided dosing study of modified FOLFIRINOX in previously untreated patients with advanced gastrointestinal malignancies. Sharma, MR., Joshi, SS., Karrison, TG., et al.[2020]

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]

References

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

Pancreatic cancer and FOLFIRINOX: a new era and new questions. [2023]

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

Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic 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. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of FOLFIRINOX: a review of studies and parameters. [2019]

6. China pubmed.ncbi.nlm.nih.gov

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

7. China pubmed.ncbi.nlm.nih.gov

Chemoradiation after FOLFIRINOX for borderline resectable or locally advanced pancreatic cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

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

A UGT1A1 genotype-guided dosing study of modified FOLFIRINOX in previously untreated patients with advanced gastrointestinal malignancies. [2020]

11. 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]