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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05610826
Recruitment Status : Not yet recruiting
First Posted : November 9, 2022
Last Update Posted : November 9, 2022
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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.


Condition or disease Intervention/treatment Phase
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) Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preoperative PRRT Versus Surgical Cytoreduction Alone in Metastatic Pancreatic Neuroendocrine Tumors to the Liver: A Phase II Multi-institutional Trial
Estimated Study Start Date : February 1, 2023
Estimated Primary Completion Date : February 1, 2027
Estimated Study Completion Date : February 1, 2027


Arm Intervention/treatment
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 tumors in the body to destroy or slow their growth and reduce disease side effects.




Primary Outcome Measures :
  1. Progression-free Survival [ Time Frame: 2 years ]
    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 :
  1. Overall Survival [ Time Frame: 2 years ]

    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. Objective Response Rate [ Time Frame: 2 Years ]
    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.

  3. Increase in Progression Free Survival [ Time Frame: 2 years ]
    To determine whether PRRT plus cytoreductive surgery increases PFS when compared to a historical cohort of patients undergoing PRRT only for metastatic PanNETs.

  4. Improvement in Progression-Free Survival (PFS2) [ Time Frame: 2 years ]
    To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves progression-free survival (PFS2)

  5. Improvement in Overall Survival [ Time Frame: 2 years ]
    To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves Overall Survival.

  6. Difference in imaging characteristics [ Time Frame: 2 years ]
    To determine differences in imaging characteristics (e.g. tumor size), biochemical and molecular signatures of patients having received surgery + PRRT or surgery alone.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05610826


Contacts
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Contact: Xavier Keutgen, MD 773-702-7125 xkeutgen@surgery.bsd.uchicago.edu

Locations
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United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: Xavier Keutgen, MD University of Chicago
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT05610826    
Other Study ID Numbers: IRB19-1485
First Posted: November 9, 2022    Key Record Dates
Last Update Posted: November 9, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Chicago:
pancreatic cancer
pancreas cancer
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Pancreatic Neoplasms
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Adenoma
Neoplasms, Glandular and Epithelial
Lutetium Lu 177 dotatate
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action