Fostamatinib + Chemotherapy for Pancreatic Cancer

Overseen By Shakeela Dad, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Diego

Disqualifiers: Prior PDAC treatment, Metastatic PDAC, Hepatitis, others

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

Compensation: Varies

Number of Visits: 6

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that you must be able to withhold or discontinue any prohibited or restricted medications during the study. It's best to discuss your specific medications with the study team.

How is the drug Fostamatinib + Chemotherapy unique for treating pancreatic cancer?

Fostamatinib is unique because it is being combined with chemotherapy for pancreatic cancer, which is different from the standard FOLFIRINOX regimen. Fostamatinib, known for treating other conditions like immune thrombocytopenia, may offer a novel mechanism of action by targeting specific pathways not addressed by traditional chemotherapy. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a Phase 1b trial evaluating the combination of Fostamatinib, a Syk kinase inhibitor currently FDA-approved for chronic idiopathic thrombocytopenia purpura (ITP), with the standard of care chemotherapy agents gemcitabine and nab-paclitaxel, for the perioperative treatment of resectable non metastatic pancreatic ductal adenocarcinoma (PDAC).

Research Team

Andrew Lowy, MD

Principal Investigator

UCSD

Eligibility Criteria

This trial is for adults with non-metastatic, resectable pancreatic cancer who can consent to treatment. They must have good performance status (ECOG ≤ 1), no metastasis or major blood vessel involvement, and be considered a surgical candidate. Those with lymphadenopathy outside the surgical area are excluded unless biopsied negative.

Inclusion Criteria

My portal and splenic veins are not blocked.

I can understand and am willing to sign the consent form.

My cancer has not significantly spread to major blood vessels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants receive fostamatinib in combination with gemcitabine and nab-paclitaxel for 4 cycles

16 weeks

3 visits per 28-day cycle (in-person)

Surgical Resection

Participants undergo pancreatic surgical resection

1 week

Postoperative Treatment

Participants receive fostamatinib in combination with gemcitabine and nab-paclitaxel for 2 cycles

8 weeks

3 visits per 28-day cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Fostamatinib

Trial Overview The study tests Fostamatinib combined with standard chemotherapy (gemcitabine and nab-paclitaxel) in patients undergoing surgery for pancreatic cancer. It's a Phase 1b trial to see how well this combination works as perioperative treatment.

Participant Groups

Group I: Fostamatinib in combination with gemcitabine/nab-paclitaxel Experimental Treatment 1 Intervention

Fostamatinib 100 mg will be taken by the study participants orally twice a day for 7 days prior to, and then during chemotherapy with gemcitabine/nab-paclitaxel. These 2 agents will be administered intravenously on days 1, 8, and 15 of each 28-day cycle.

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Rigel Pharmaceuticals

Industry Sponsor

Trials

37

Recruited

4,000+

Findings from Research

In a study of 97 patients with advanced pancreatic adenocarcinoma treated with FOLFIRINOX, baseline splenomegaly was found to predict poorer progression-free survival (PFS) and overall survival (OS), indicating its potential as a biomarker for treatment response.

The predictive model, which included factors like performance status and liver metastasis, showed strong efficacy in predicting outcomes for patients treated with FOLFIRINOX, with an area under the curve (AUC) of 0.81, confirming the importance of splenic volume in clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline splenic volume as a surrogate marker of FOLFIRINOX efficacy in advanced pancreatic carcinoma. Aarnink, A., Richard, C., Truntzer, C., et al.[2022]

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]

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]

FOLFIRINOX treatment in metastatic pancreatic carcinoma showed a median overall survival of 10 months, with similar efficacy whether used in first- or second-line therapy, indicating its effectiveness as a treatment option.

Patients with tumors located in the head of the pancreas had a poorer prognosis, with a median survival of only 8 months, compared to 14 months for those with tumors in the body or tail, highlighting the importance of tumor location in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influcence of localization of primary tumor on effectiveness of 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) in patients with metastatic pancreatic adenocarcinoma: a retrospective study. Lorgis, V., Chauffert, B., Gentil, J., et al.[2022]

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]

References

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

Baseline splenic volume as a surrogate marker of FOLFIRINOX efficacy in advanced pancreatic carcinoma. [2022]

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

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

3. 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]

4. Greece pubmed.ncbi.nlm.nih.gov

Influcence of localization of primary tumor on effectiveness of 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) in patients with metastatic pancreatic adenocarcinoma: a retrospective study. [2022]

5. China pubmed.ncbi.nlm.nih.gov

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