Perioperative Fostamatinib With Gemcitabine and Nab-paclitaxel in Resectable Pancreatic Cancer

NCT06639724 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 810834
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Pancreatic Ductal Adenocarcinoma (PDAC)

Keywords

PDAC; Pancreatic cancer; chemotherapy; Syk kinase inhibitor; Phase 1b; pancreatectomy; biomarkers; tumor microenvironment; non metastatic

Outcome Measures

Primary Outcomes (1)

• Surgical delay

  Number and percentage of participants who experience surgical delay, as measured by the proportion of enrolled participants for whom pancreatic resection cannot be performed within 6 weeks of the last pre-operative treatment cycle.

  6 weeks from the last pre-operative treatment cycle

Study Arms (1)

Fostamatinib in combination with gemcitabine/nab-paclitaxel

EXPERIMENTAL

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.

Combination Product: Fostamatinib in combination with chemotherapy (gemcitabine and nab-paclitaxel)

Interventions

Fostamatinib in combination with chemotherapy (gemcitabine and nab-paclitaxel) COMBINATION_PRODUCT

Fostamatinib is a Syk kinase inhibitor currently FDA-approved for chronic idiopathic thrombocytopenia purpura but it has not been studied in PDAC. The investigators hypothesize that Syk inhibition reprograms macrophages to an immunostimulatory phenotype in the tumor microenvironment. Thus, Syk inhibition with fostamatinib in combination with chemotherapy could improve outcomes for patients with PDAC while having a favorable safety profile.

Fostamatinib in combination with gemcitabine/nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has the ability to understand and willingness to sign a written informed consent.
• Patient is ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Patient must have surgical consult to verify patient is a surgical candidate within 28 days prior to enrollment.
• 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:
• No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (and, if present, replaced right hepatic artery).
• No involvement, or \< 180° interface between tumor and vessel wall, of the portal vein and/or superior mesenteric vein.
• Patent portal vein/splenic vein confluence.
• No evidence of metastatic disease.
• 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.
• For tumors of the body and tail of the pancreas, involvement of the splenic artery and vein of any degree is considered resectable disease.
• Patient has adequate organ function as defined below:
• Absolute Neutrophil Count ≥ 1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L.
• Hemoglobin ≥ 9.0 g/dL

You may not qualify if:

• Any prior treatment for PDAC.
• Recurrent or metastatic PDAC.
• Peripheral neuropathy \> grade 2
• Received an investigational agent within 28 days prior to the first dose of study drug.
• 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).
• Active infection requiring systemic therapy.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• History of receiving a solid organ transplant or allogeneic bone marrow transplant.
• Major surgical procedure within 28 days prior to the first dose of study drug.
• Unable or unwilling to withhold or discontinue any prohibited or restricted medications/procedures for the specified windows during the study.
• Pregnancy or lactation.

Sponsors & Collaborators

• University of California, San Diego: lead
• Rigel Pharmaceuticals: collaborator

Study Sites (1)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

Related Publications (1)

• Rohila D, Park IH, Pham TV, Weitz J, Hurtado de Mendoza T, Madheswaran S, Ishfaq M, Beaman C, Tapia E, Sun S, Patel J, Tamayo P, Lowy AM, Joshi S. Syk Inhibition Reprograms Tumor-Associated Macrophages and Overcomes Gemcitabine-Induced Immunosuppression in Pancreatic Ductal Adenocarcinoma. Cancer Res. 2023 Aug 15;83(16):2675-2689. doi: 10.1158/0008-5472.CAN-22-3645.

  PMID: 37306759 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

fostamatinib; Drug Therapy; Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Andrew Lowy, MD

  UCSD

  STUDY CHAIR

Central Study Contacts

Hitendra Patel, MD

CONTACT

858-822-5354; CancerCTO@health.ucsd.edu

Shakeela Dad, PhD

CONTACT

858-822-5354; CancerCTO@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: October 15, 2024
• Study Start: December 5, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)