PROACTIVE: Surgical Resection Outcomes in Locally Advanced and Unresectable Pancreatic Cancer After Neoadjuvant Chemotherapy

Locally Advanced Pancreatic Adenocarcinoma Clinical Trial

Official title:

PROACTIVE Pilot Study: Pancreatic Resection Outcomes in Locally Advanced Pancreatic Cancer Involving Visceral Arteries Treated With Neoadjuvant Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06132087
• Other study ID #: 3P-23-5
• Secondary ID: NCI-2023-092103P
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: December 1, 2028

Study information

• Verified date: May 2024
• Source: University of Southern California
• Contact: Charlean Ketchens, RN
• Phone: 323-865-3035
• Email: ketchens_c[@]med.usc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial tests how well surgical resection after chemotherapy given before surgery to make the tumor smaller (neoadjuvant) works to treat pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) and that cannot be removed by surgery (unresectable). In general, surgery is considered the most effective treatment for pancreatic cancer, especially when the cancer is localized and has not spread to other organs. However, most patients with pancreatic cancer are not candidates for surgical removal because the cancer has grown into or close to nearby arteries, veins, or organs and there is a concern of damaging these nearby structures. Researchers want to find out if surgery after neoadjuvant chemotherapy can be done safely to completely remove the tumor in patients with locally advanced and unresectable pancreatic cancer.

Description:

PRIMARY OBJECTIVE:

I. Evaluate the R0 resection in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

SECONDARY OBJECTIVES:

I. To evaluate overall survival (OS) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

II. To measure disease free survival (DFS) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

III. To evaluate the correlation between post-neoadjuvant/preoperative radiological staging and pathologic staging.

IV. To estimate time to distant metastases (TDM) in patients in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

EXPLORATORY OBJECTIVES:

I. To evaluate the correlation between post-neoadjuvant/preoperative radiological staging and pathologic staging.

II. To evaluate objective response rate (ORR) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy.

III. To assess if mutations on next-generation sequencing (NGS) testing and the change in circulating tumor deoxyribonucleic acid (ctDNA) pre- and post-operative is predictive of DFS or OS in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

IV. To evaluate the rate of unresectability in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy.

V. To evaluate pathologic tumor response and rate of pathologic complete response (pCR) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

VI. To evaluate correlation between R0 resection rate and pathologic treatment response and survival outcomes.

VII. To evaluate number of cycles of perioperative chemotherapy received in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

VIII. To evaluate the adverse event profile in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

IX. To evaluate the physical functioning, nausea/vomiting, and diarrhea, as measured with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

X. To evaluate the average operative time in minutes in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

XI. To evaluate the estimated blood loss (mL) in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

XII. To assess the length of hospital, stay in for patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

XIII. To evaluate the incidence of thrombosis in patients with locally advanced pancreatic adenocarcinoma treated with perioperative chemotherapy and surgery.

OUTLINE:

Patients undergo laparoscopy followed by surgical resection with pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy at the discretion of the surgeon within 2-8 weeks following completion of standard of care neoadjuvant chemotherapy regimen. Patients undergo computed tomography (CT) and blood sample collection throughout the study and/or magnetic resonance imaging (MRI) during screening. Patients also undergo tissue collection at time of surgical resection on study.

After completion of study intervention, patients are followed up at 30 days, every 3 months for the first year, then every 6 months until 2 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 1, 2028
• Est. primary completion date: December 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic or cytologic proof of pancreatic adenocarcinoma

• Locally advanced, stage III (T4NxM0) and unresectable by National Comprehensive Cancer Network (NCCN) Guidelines prior to perioperative chemotherapy

• Patients must have measurable disease at diagnosis per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

• At least 4 cycles of perioperative chemotherapy (gemcitabine [Gem]/nab-paclitaxel or fluorouracil, irinotecan, leucovorin and oxaliplatin [FOLFIRINOX]) received with no evidence of progression on restaging scans per RECIST 1.1

• Age = 18 years

• Performance status Eastern Cooperative Oncology Group (ECOG) 0-1

• Absolute neutrophil count = 1,500/mcL

• Platelets = 100,000/mcl

• Total bilirubin = 1.5 x institutional upper limit of normal (ULN) if no biliary stenting has been done or 2.0 x ULN if patient is status post (s/p) biliary stenting or two down trending values

• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SPGT]) = 2.5 X ULN

• Creatinine (Cr) = 1.5 mg/dL or Cr clearance = 30 mL/min (as estimated by Cockcroft Gault)

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

• Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

• Patient with known distant metastases

• Patients who have not recovered from adverse events of chemotherapy due to agents administered more than 4 weeks earlier

• Patients who have progressed on 2 prior systemic chemotherapy lines or received prior radiotherapy for pancreatic cancer

• Patients may not be receiving any other investigational agents

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Pancreatic Adenocarcinoma
• Pancreatic Neoplasms
• Unresectable Pancreatic Adenocarcinoma

Intervention

Procedure:
• Biospecimen Collection
Undergo blood and tissue sample collection
• Computed Tomography
Undergo CT
• Distal Pancreatectomy
Undergo distal pancreatectomy
• Laparoscopy
Undergo laparoscopy
• Magnetic Resonance Imaging
Undergo MRI
• Pancreaticoduodenectomy
Undergo pancreaticoduodenectomy

Other:
• Questionnaire Administration
Ancillary studies

Procedure:
• Surgical Procedure
Undergo surgical resection
• Total Pancreatectomy
Undergo total pancreatectomy

Locations

Country	Name	City	State
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R0 resection rate	Will be defined as the proportion of patients with negative resection margins after undergoing surgery.	At time of surgery
Secondary	Overall survival	Determined from the date of registration to the date of death due to any cause.	Up to 2 years
Secondary	Disease-free survival	Determined from the date of registration to the date of progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to any cause, whichever occurs first.	Up to 2 years
Secondary	Time to locoregional recurrence	Determined from the date of registration to the date of locoregional recurrence after resection.	Up to 2 years
Secondary	Time to distant metastases	Determined from the date of registration to the date of metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection.	Up to 2 years