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

NCT05610826 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: IRB19-1485
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Neuroendocrine Tumor; Pancreas Cancer

Keywords

pancreatic cancer; pancreas cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Survival

  2 years

• Objective Response Rate

  2 Years

• Increase in Progression Free Survival

  2 years

• Improvement in Progression-Free Survival (PFS2)

  2 years

• Improvement in Overall Survival

  2 years

Study Arms (2)

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

OTHER

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

Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)

EXPERIMENTAL

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

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

Interventions

cytoreductive surgery PROCEDURE

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

Arm 1- Control Arm - Standard Of Care - no peptide receptor radionuclide therapy; Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)

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

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.

Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)

Peptide receptor radionuclide therapy (PRRT) PROCEDURE

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.

Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).
• \. 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.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

The University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Adenoma, Islet Cell; Pancreatic Neoplasms

Interventions

Cytoreduction Surgical Procedures

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Xavier Keutgen, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: November 9, 2022
• Study Start: March 7, 2023
• Primary Completion: September 11, 2024
• Study Completion: September 11, 2024
• Last Updated: October 26, 2024

Record last verified: 2024-01

Locations

US (1)