Endoscopic Ultrasound Radiofrequency Ablation and Immunotherapy Pembrolizumab for Locally Advanced Unresectable and Metastatic Pancreatic Duct Adenocarcinoma

NCT06831136 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: HSC-MS-24-0437
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to perform a pilot phase II trial to evaluate the safety and efficacy of combined EUS-RFA, chemotherapy, and systemic immunotherapy (pembrolizumab) for the treatment of locally advanced unresectable and metastatic Pancreatic ductal adenocarcinoma (mPDAC).

Conditions

Pancreatic Ductal Adenocarcinoma

Keywords

metastatic cancer; chemotherapy; systemic immunotherapy; pembrolizumab; neoplasms; Endoscopic Ultrasound Radiofrequency ablation (EUS-RFA)

Outcome Measures

Primary Outcomes (1)

• Efficacy as assessed by the Overall response rate using RECIST v1.1 guidelines

  (ORR) is defined as proportion of patients with complete response (CR) or partial response (PR)

  From date of diagnosis to the initial date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months.

Secondary Outcomes (7)

• Incidence of adverse events (AEs)

  From the date of the initiation of study treatment until 30 days after the last dose of study treatment, withdrawal of consent, or study termination

• Incidence of serious adverse events (SAEs)

  From the date of the initiation of study treatment until 30 days after the last dose of study treatment, withdrawal of consent, or study termination

• Duration of response (DOR)

  Every 8 weeks from the time of enrollment to the date of death due to any causes for up to 5 years

• Progression-free survival (PFS)

  Every 8 weeks from the time of enrollment to the date of death due to any causes for up to 5 years

• Overall survival (OS)

  Every 8 weeks from the time of enrollment to the date of death due to any causes for up to 5 years

Study Arms (1)

Standard of care chemotherapy + immunotherapy + EUS-RFA

EXPERIMENTAL

Drug: Neoadjuvant Chemotherapy (NAC); Drug: Immunotherapy (pembrolizumab); Device: Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA)

Interventions

Neoadjuvant Chemotherapy (NAC) DRUG

Participant will undergo 8 weeks of NAC (treating physician's choice). Possible regimens are either mFOLFIRINOX or NALIRIFOX or Gemcitabine Nab-Paclitaxel ± Cisplatin (GA+/-Cisplatin) or Capecitabine (Xeloda).

Standard of care chemotherapy + immunotherapy + EUS-RFA

Immunotherapy (pembrolizumab) DRUG

2-12 weeks after initial chemotherapy and after the first EUS-RFA treatment, patients will receive 400 mg every 6 weeks of pembrolizumab via infusion. Participants will be administered standard of care chemotherapy and pembrolizumab every 6 weeks.

Standard of care chemotherapy + immunotherapy + EUS-RFA

Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) DEVICE

After 2-12 weeks of chemotherapy, patients will undergo EUS-RFA treatment 1 session every 6 weeks. Each RFA treatment will be for up to 5 cycles at 30W for 20 seconds or until there is an increase in measured impedance. After the 5th EUS-RFA, if there is clinical benefit, then patients will continue with EUS-RFA treatments until no active tumor is seen. During each session, the therapeutic gastroenterologist will evaluate if there is any tumor to undergo RFA. If no active tumor seen, then will abort RFA

Standard of care chemotherapy + immunotherapy + EUS-RFA

Eligibility Criteria

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

You may qualify if:

• Is willing and able to comply with the protocol for the duration of the study,including undergoing treatment and scheduled visits and examinations, including follow-up
• Biopsy-proven locally advanced unresectable or metastatic PDAC
• Patients who have undergone prior resection will be excluded unless there is recurrent pancreatic tumor that is amenable to EUS-RFA.
• If biliary metal stent is placed, during procedure of EUS-RFA, indwelling biliary metal stent will be removed during initial EUS-RFA and then replaced with plastic stent.
• Mental capacity to provide informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
• At least one measurable metastatic lesion on axial imaging per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
• No prior systemic therapy, including chemotherapy or chemoradiation is permitted with the following exceptions:
• Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for pancreatic adenocarcinoma is permitted if standard of care neoadjuvant or adjuvant therapy was completed at least 3 months prior to study enrollment. Prior adjuvant therapy may include mFFX, NALIRIFOX, GA or Capecitabine (Xeloda).
• If started on first-line treatment for mPDAC elsewhere (i.e., not at our study site), eligible participants can have undergone 3 months of chemotherapy with stable disease before study entry. Note: Imaging done outside the site will need to be reviewed for a 2nd opinion to confirm stable disease.
• i. For patients who had prior treatment and stable disease up to 3 months and confirmed radiographically by our radiology investigators, then patients can proceed with EUS-RFA within 6-8 weeks of enrollment of study.
• c. Patients who have started chemotherapy within a 3-month timeframe are allowed.
• Absolute neutrophil count (ANC) ≥1 x 109/L
• Platelet count ≥75 x 109/L
• Albumin levels ≥3 g/dL

You may not qualify if:

• No telephone number and permanent street address
• Pregnant or breastfeeding patients; or is a male or female patient of reproductive potential who is not willing to employ effective birth control from time of screening to 90 days after the last dose
• Inmates or prisoners
• Unable to provide informed consent
• Resectable, borderline resectable PDAC.
• Known history of central nervous system (CNS) metastases
• Has a history of another primary malignancy. Patients having the following are still eligible:
• No active stage 4 cancer
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Known low or absent dihydropyrimidine dehydrogenase (DPD) activity
• Use of strong inhibitors or inducers of Cytochrome P450 3A (CYP3A), CYP2C8 and UGT1A1
• History or evidence of clinically significant or uncontrolled cardiovascular, CNS,and/or other systemic disease that in the investigator's opinion would preclude participation in the study or compromise the patient's ability to give informed consent
• History of HIV or active tuberculosis (TB) (PPD response without active TB is allowed)
• Underlying medical conditions that, in the Investigator's opinion, will make the administration of pembrolizumab hazardous (e.g., interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms)

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

Neoadjuvant Therapy; Immunotherapy; pembrolizumab; Endosonography

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Immunomodulation; Biological Therapy; Ultrasonography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Putao Cen

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Putao Cen, MD

CONTACT

(832) 325-7705; pancreasresearch@uth.tmc.edu

Ayodeji Adeniji

CONTACT

(713) 500-5377; Ayodeji.Adeniji@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: February 17, 2025
• Study Start: March 26, 2025
• Primary Completion (Estimated): January 20, 2028
• Study Completion (Estimated): January 20, 2030
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)