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

Primary Purpose

Pancreatic Neuroendocrine Tumor, Pancreas Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cytoreductive surgery
Lutathera - a small molecule used in Peptide Receptor Radionuclide Therapy (PRRT)
Peptide receptor radionuclide therapy (PRRT)
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Neuroendocrine Tumor focused on measuring pancreatic cancer, pancreas cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 history of chemotherapy for 4 weeks prior to enrollment (both patients with stable disease as well as those with tumor progression under other therapies will be enrolled). Exclusion Criteria: Patient with G3 or poorly differentiated NET (grade 3, Ki-67 >20%) Previous liver-directed therapy with Yttrium-90/TACE/TAE Previous systemic therapy with Capecitabine and/or Temozolomide 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

Sites / Locations

  • The University of Chicago Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

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

Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)

Arm Description

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).

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
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.
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)
Improvement in Overall Survival
To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves Overall Survival.
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.

Full Information

First Posted
November 2, 2022
Last Updated
June 5, 2023
Sponsor
University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT05610826
Brief Title
Preoperative PRRT Versus Surgical Cytoreduction in Metastatic Pancreatic Neuroendocrine Tumors to the Liver
Official Title
Preoperative PRRT Versus Surgical Cytoreduction Alone in Metastatic Pancreatic Neuroendocrine Tumors to the Liver: A Phase II Multi-institutional Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 7, 2023 (Actual)
Primary Completion Date
February 1, 2027 (Anticipated)
Study Completion Date
February 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neuroendocrine Tumor, Pancreas Cancer
Keywords
pancreatic cancer, pancreas cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1- Control Arm - Standard Of Care - no peptide receptor radionuclide therapy
Arm Type
Other
Arm Description
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).
Arm Title
Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)
Arm Type
Experimental
Arm Description
Arm 2 will undergo four cycles of peptide receptor radionuclide therapy (PRRT) before cytoreductive surgery.
Intervention Type
Procedure
Intervention Name(s)
cytoreductive surgery
Intervention Description
Cytoreductive surgery is an operation to remove as much tumor tissue as possible.
Intervention Type
Drug
Intervention Name(s)
Lutathera - a small molecule used in Peptide Receptor Radionuclide Therapy (PRRT)
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Peptide receptor radionuclide therapy (PRRT)
Intervention Description
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 tumors in the body to destroy or slow their growth and reduce disease side effects.
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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
Time Frame
2 years
Title
Objective Response Rate
Description
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.
Time Frame
2 Years
Title
Increase in Progression Free Survival
Description
To determine whether PRRT plus cytoreductive surgery increases PFS when compared to a historical cohort of patients undergoing PRRT only for metastatic PanNETs.
Time Frame
2 years
Title
Improvement in Progression-Free Survival (PFS2)
Description
To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves progression-free survival (PFS2)
Time Frame
2 years
Title
Improvement in Overall Survival
Description
To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves Overall Survival.
Time Frame
2 years
Title
Difference in imaging characteristics
Description
To determine differences in imaging characteristics (e.g. tumor size), biochemical and molecular signatures of patients having received surgery + PRRT or surgery alone.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 history of chemotherapy for 4 weeks prior to enrollment (both patients with stable disease as well as those with tumor progression under other therapies will be enrolled). Exclusion Criteria: Patient with G3 or poorly differentiated NET (grade 3, Ki-67 >20%) Previous liver-directed therapy with Yttrium-90/TACE/TAE Previous systemic therapy with Capecitabine and/or Temozolomide 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xavier Keutgen, MD
Phone
773-702-7125
Email
xkeutgen@surgery.bsd.uchicago.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xavier Keutgen, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cancer Clinical Trials Office
Phone
855-702-8222
Email
cancerclinicaltrials@bsd.uchicago.edu

12. IPD Sharing Statement

Learn more about this trial

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

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