Preoperative PRRT Versus Surgical Cytoreduction In Metastatic Pancreatic Neuroendocrine Tumors To The Liver

Study Overview

Preoperative PRRT Versus Surgical Cytoreduction in Metastatic Pancreatic Neuroendocrine Tumors to the Liver

Doctors and researchers leading this study hope to learn more about peptide receptor radionuclide therapy (PRRT) in combination with cytoreduction (surgically removing tumors). They hope to learn if combining PRRT in combination with cytoreduction would be more effective than cytoreduction alone. PRRT itself is approved by the U.S. Food and Drug Administration (FDA) for people with PanNETs however the combination with cytoreduction is considered experimental. Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT. PRRT is a form of targeted treatment (think of a "lock and key") done by the use of a small molecule (Lutathera) Lutathera acts as a "key" to "lock" onto certain areas your tumor cells called receptors when injected into a vein and travels through the bloodstream. Lutetium-177 is the radionuclide in Lutathera which is a chemical that delivers strong radiation directly into your tumor cells and works by causing death of the cancerous tissues. PRRT can only be done on patients who have tumors that have the somatostatin receptors. Before being given PRRT, your treating doctor will run imaging tests to make sure your tumors have these targeted receptors. Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT. Participants will be randomized (like the flip of a coin) to one of two arms. Arm 1 is the control arm, which will undergo standard of care cytoreductive surgery (for the tumor). Arm 2 will undergo four cycles of PRRT before cytoreductive surgery.

Pancreatic Neuroendocrine Tumor
Pancreas Cancer

PROCEDURE: cytoreductive surgery
DRUG: Lutathera - a small molecule used in Peptide Receptor Radionuclide Therapy (PRRT)
PROCEDURE: Peptide receptor radionuclide therapy (PRRT)

IRB19-1485

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-11-02	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-01-26
First Submitted that Met QC Criteria 2022-11-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-01-29
First Posted (ACTUAL) 2022-11-09	Results First Posted N/A	Last Verified 2024-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
OTHER: Arm 1- Control Arm - Standard Of Care - no peptide receptor radionuclide therapy Arm 1 is the control arm, which will undergo standard of care cytoreductive surgery (for the tumor). Participants in this arm will not receive peptide receptor radionuclide therapy (PRRT).	PROCEDURE: cytoreductive surgery Cytoreductive surgery is an operation to remove as much tumor tissue as possible.
EXPERIMENTAL: Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery) Arm 2 will undergo four cycles of peptide receptor radionuclide therapy (PRRT) before cytoreductive surgery.	PROCEDURE: cytoreductive surgery Cytoreductive surgery is an operation to remove as much tumor tissue as possible. DRUG: Lutathera - a small molecule used in Peptide Receptor Radionuclide Therapy (PRRT) PRRT is a form of targeted treatment (think of a "lock and key") done by the use of a small molecule (Lutathera). Lutathera acts as a "key" to "lock" onto certain areas your tumor cells called receptors when injected into a vein and travels through blood. PROCEDURE: Peptide receptor radionuclide therapy (PRRT) PRRT is a molecular targeted therapy used to treat neuroendocrine tumors (NET). Molecular targeted therapies use drugs or other substances to identify and attack cancer cells while reducing harm to healthy tissue. PRRT delivers high doses of radiation to

Participant Group/Arm

Intervention/Treatment

OTHER: Arm 1- Control Arm - Standard Of Care - no peptide receptor radionuclide therapy

Arm 1 is the control arm, which will undergo standard of care cytoreductive surgery (for the tumor). Participants in this arm will not receive peptide receptor radionuclide therapy (PRRT).

PROCEDURE: cytoreductive surgery

Cytoreductive surgery is an operation to remove as much tumor tissue as possible.

EXPERIMENTAL: Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)

Arm 2 will undergo four cycles of peptide receptor radionuclide therapy (PRRT) before cytoreductive surgery.

PROCEDURE: cytoreductive surgery

Cytoreductive surgery is an operation to remove as much tumor tissue as possible.

DRUG: Lutathera - a small molecule used in Peptide Receptor Radionuclide Therapy (PRRT)

PRRT is a form of targeted treatment (think of a "lock and key") done by the use of a small molecule (Lutathera). Lutathera acts as a "key" to "lock" onto certain areas your tumor cells called receptors when injected into a vein and travels through blood.

PROCEDURE: Peptide receptor radionuclide therapy (PRRT)

PRRT is a molecular targeted therapy used to treat neuroendocrine tumors (NET). Molecular targeted therapies use drugs or other substances to identify and attack cancer cells while reducing harm to healthy tissue. PRRT delivers high doses of radiation to

Primary Outcome Measures	Measure Description	Time Frame
Progression-free Survival	To determine whether preoperative peptide receptor radionuclide therapy (PRRT) prior to hepatic cytoreduction increases progression free survival (PFS1) (when compared to cytoreduction alone) in patients with metastatic PanNETs to the liver	2 years

Secondary Outcome Measures	Measure Description	Time Frame
Overall Survival	To determine whether preoperative peptide receptor radionuclide therapy (PRRT) prior to hepatic cytoreduction increases overall survival. (when compared to cytoreduction alone) in patients with metastatic PanNETs to the liver	2 years
Objective Response Rate	To determine whether preoperative peptide receptor radionuclide therapy (PRRT) induces a significant objective response rate (according to RECIST) in the primary tumor (if available) and hepatic metastases of patients with metastatic PanNETs to the liver, thus facilitating surgical resection.	2 Years
Increase in Progression Free Survival	To determine whether PRRT plus cytoreductive surgery increases PFS when compared to a historical cohort of patients undergoing PRRT only for metastatic PanNETs.	2 years
Improvement in Progression-Free Survival (PFS2)	To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves progression-free survival (PFS2)	2 years
Improvement in Overall Survival	To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves Overall Survival.	2 years
Difference in imaging characteristics	To determine differences in imaging characteristics (e.g. tumor size), biochemical and molecular signatures of patients having received surgery + PRRT or surgery alone.	2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Xavier Keutgen, MD

Phone Number: 773-702-7125

Email: [email protected]

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Metastatic Pancreatic neuroendocrine tumors (PanNET) to the liver
Well- or moderately differentiated (grade 1 or grade 2, Ki-
Ability to aim for equal or greater than 90% hepatic cytoreduction surgically
Proof of SSTR2 expression by uptake of tumor on 68Ga DOTATATE PET CT (Krenning Score on all or a majority of lesions
Age older than 18 years
No Somatostatin Analogues (SSA) or other systemic therapy for 4 weeks prior to starting PRRT, if randomized to arm 2.

Patient with G3 or poorly differentiated NET (grade 3, Ki-67 >20%)
Previous liver-directed therapy with Yttrium-90 (TACE/TAE allowed if performed more than 12 months prior to enrollment)
Systemic therapy with Capecitabine and/or Temozolamide within 12 months of enrollment.
No tumor uptake on 68Ga DOTATATE PET CT
Liver tumor burden > 50% (as defined by CT or MRI)
Signs of early liver failure (T-Bilirubin >3, INR > 1.5, Albumin <3.0 g/dL unless prothrombin time is within the normal range) or cirrhosis or ascites
calculated by the Cockroft Gault method, eventually confirmed by measured creatinine clearance
(or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma
camera-based) <50 mL/min (the measured creatinine clearance / GFR is required only as - confirmatory exam).
2. Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L - (75x103/mm3).
Known brain metastases, unless these metastases have been treated and stabilized.
Uncontrolled congestive heart failure (NYHA II, III, IV).
Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
Pregnancy or lactation.
For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel). - Prior external beam radiation therapy to more than 25% of the bone marrow.
Current spontaneous urinary incontinence making impossible the safe administration of the radioactive IMP.
Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and with no evidence of recurrence.
Patients who have not provided a signed informed consent form to accept this treatment.
Poor renal function
Quality Unit language added
editorial changes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Xavier Keutgen, MD, University of Chicago

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record