Combining Fostamatinib with Gemcitabine and Nab-paclitaxel for Pancreatic Cancer Treatment

A Phase 1b Trial of Perioperative Fostamatinib With Gemcitabine and Nab-paclitaxel in Resectable Pancreatic Cancer

This study is testing if adding a new drug called Fostamatinib to standard chemotherapy can help improve treatment outcomes for patients with operable pancreatic cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Diego (Academic / other)
• Drugs / interventions: Fostamatinib, chemotherapy
• Locations: 1 site (La Jolla, California)
• Trial ID: NCT06639724 on ClinicalTrials.gov

What this trial studies

This Phase 1b trial evaluates the use of Fostamatinib, a Syk kinase inhibitor, alongside standard chemotherapy agents gemcitabine and nab-paclitaxel for patients with resectable pancreatic ductal adenocarcinoma (PDAC). The study aims to enhance anti-tumor immunity by reprogramming tumor-associated macrophages, based on promising preclinical findings. Participants will receive four cycles of treatment before surgery and two cycles after, with long-term follow-up to assess safety and efficacy. The goal is to determine if this combination can improve outcomes for patients undergoing surgery for PDAC.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with resectable pancreatic ductal adenocarcinoma and an ECOG performance status of 1 or lower.

Not a fit: Patients with unresectable pancreatic cancer or those with significant comorbidities that affect surgical candidacy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with resectable pancreatic cancer.

How similar studies have performed: While the combination of Syk kinase inhibitors with chemotherapy is a novel approach in PDAC, previous studies have shown promise in preclinical models, indicating potential for success in this patient population.

Eligibility criteria

Inclusion Criteria:

1. Patient has the ability to understand and willingness to sign a written informed consent.
2. Patient is ≥ 18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
4. Patient must have surgical consult to verify patient is a surgical candidate within 28 days prior to enrollment.
5. Patient must have resectable primary PDAC based on contrast-enhanced CT or MRI of the chest, abdomen, and pelvis performed no more than 4 weeks before enrollment/baseline. Note that if CT or MRI was performed more than 4 weeks before this visit, imaging needs to be repeated to evaluate eligibility in the study. Resectable primary tumor is defined as:

   1. No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (and, if present, replaced right hepatic artery).
   2. No involvement, or \< 180° interface between tumor and vessel wall, of the portal vein and/or superior mesenteric vein.
   3. Patent portal vein/splenic vein confluence.
   4. No evidence of metastatic disease.
   5. Lymphadenopathy (defined as nodes measuring \> 1cm in short axis) outside the surgical basin (i.e., para- aortic, peri-caval, celiac axis, or distant nodes) is considered M1 disease and makes the patient ineligible. If, however, such nodes are biopsied and are negative, then enrollment can be considered after review with the study principal investigator (PI) and/or co-investigator.
   6. For tumors of the body and tail of the pancreas, involvement of the splenic artery and vein of any degree is considered resectable disease.
6. Patient has adequate organ function as defined below:

   1. Absolute Neutrophil Count ≥ 1.5 x 10\^9/L
   2. Platelet count ≥ 100 x 10\^9/L.
   3. Hemoglobin ≥ 9.0 g/dL
   4. aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SPGT) ≤ 2.5 X institutional upper limit of normal (ULN)
   5. Total Bilirubin ≤ 1.5 x institutional ULN or ≤3 × institutional ULN in Gilbert's Ds
   6. Serum creatinine ≤ 2 x institutional ULN
7. For subjects able to become pregnant: use of highly effective contraception for at least 2 weeks prior to enrollment and agreement to use such a method during study participation.
8. For subjects able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner during study participation.

Exclusion Criteria:

1. Any prior treatment for PDAC.
2. Recurrent or metastatic PDAC.
3. Peripheral neuropathy \> grade 2
4. Received an investigational agent within 28 days prior to the first dose of study drug.
5. History of Hepatitis B (defined as Hepatitis B surface antigen, HBsAg, reactive) or known active Hepatitis C virus (HCV) (defined as HCV RNA - qualitative - is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. (Individuals who are hepatitis C antibody positive may be enrolled if negative viral load confirmed).
6. Active infection requiring systemic therapy.
7. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
8. History of receiving a solid organ transplant or allogeneic bone marrow transplant.
9. Major surgical procedure within 28 days prior to the first dose of study drug.
10. Unable or unwilling to withhold or discontinue any prohibited or restricted medications/procedures for the specified windows during the study.
11. Pregnancy or lactation.

Where this trial is running

La Jolla, California

• University of California, San Diego Moores Cancer Center — La Jolla, California, United States (Recruiting)

Study contacts

• Study coordinator: Hitendra Patel, MD

Conditions Pancreatic Ductal Adenocarcinoma; PDAC; Pancreatic cancer; chemotherapy; Syk kinase inhibitor; Phase 1b; pancreatectomy; biomarkers