Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery

Neuroendocrine Tumors Clinical Trial

Official title: A Phase II Trial of Mutation-Targeted Therapy With Sunitinib or Everolimus in Patients With Advanced Low-or Intermediate Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery

Status Terminated

Clinical Trial Summary

Background:

• Neuroendocrine tumors (NETs) come from cells of the hormonal and nervous systems. Some people have surgery to shrink the tumor. Sometimes the tumors come back. Researchers think that treatment with drugs based on knowing the defective gene might give better results.

Objective:

• To see if drugs selected based on the defective gene result in better tumor response. The drugs are Sunitinib and Everolimus.

Eligibility:

• People age 18 and older with an advanced low- or intermediate-grade gastrointestinal or pancreatic neuroendocrine tumor.

Design:

• Participants will be screened with:

• Medical history

• Physical exam

• Scans

• Blood, urine, and lab tests

• The study team will see if participants should have surgery.

• If yes, participants will:

• Sign a separate consent

• Have computed tomography (CT) scan before and after surgery

• Have as much of the tumor removed as possible. A small piece will be tested for mutation type.

• If no, participants will have a small piece of tumor removed for the testing.

• If the surgery might cure them, the participant will leave the study. The other participants will be assigned to take either Sunitinib or Everolimus.

• Participants will take their drug by mouth once a day. They will keep a medicine diary. Some will keep track of their blood pressure at least weekly.

• Screening tests may be repeated at study visits. Participants also may have their heart evaluated.

• About 30 days after the last day of their study drug, participants will have a follow-up visit that repeats the screening tests.

• Participants will be contacted every 3 months after this visit.

Clinical Trial Description

Background:

• Neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas are a rare and heterogeneous group of neoplasms with unique tumor biology, natural history, and clinical management issues.

• Most NETs are sporadic, but they can be part of familial cancer syndromes such as multiple endocrine neoplasia type 1 (MEN1), neurofibromatosis type 1 (NF1) or Von Hippel-Lindau (VHL) syndrome.

• Well-differentiated, low or intermediate grade NETs have a heterogeneous natural history.

• Surgery is the only curative treatment option in patients with localized early stage NETs.

• The optimal management strategy for patients with advanced NETs is unknown.

• The majority of NETs have somatic mutations in MEN1 and cyclin dependent kinase inhibitor 1B (CDKN1B), and genes involved in the phosphatidylinositol-3-kinase (PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway, and/or overexpression of growth factors and their receptors such as vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor (PDGF), and platelet-derived growth factor receptors (PDGFR) that can be targeted for therapy.

• Survival in patients with NETs and somatic mutations is better than patients with wild type NETs.

• Sunitinib (multi-tyrosine kinase inhibitor) and Everolimus (mTOR signaling pathway inhibitor) are currently approved for the treatment of progressive, unresectable, locally advanced or metastatic pancreatic NETs.

• However, mutation targeted therapy with Sunitinib or Everolimus has not been studied in this patient population.

• The present proposal aims to determine if mutation targeting therapy for patients with advanced low- or intermediate grade NETs is more effective than historically expected results.

Objectives:

-To determine the progression-free survival in patients with NETs of the gastrointestinal tract and pancreas treated with Sunitinib or Everolimus based on tumor genotyping.

Eligibility:

-Patients with:

• progressive, histologically or cytologically diagnosed low or intermediate grade locally advanced or metastatic NETs.

• Age greater than or equal to 18 years

Design:

• Phase II open labeled clinical trial.

• Tumor biopsy for tumor genotyping will be performed if the patient does not have archival tissue available and does not have MEN1, VHL or NF1.

• Patients with somatic or germline mutations in MEN1/PDGFR/KIT/FMS-like tyrosine kinase-3 will be treated with Sunitinib. (Arm 1)

• Patients with somatic/germline mutations in NF1/PTEN/PI3K/AKT/mTOR/VHL will be treated with Everolimus. (Arm 2)

• Patients with wildtype tumor will be treated with Sunitinib. (Arm 1)

• Patients who have disease-progression on either Sunitinib or Everolimus will cross-over to the other drug.

• Treatment will continue until disease progression, unacceptable toxicity, or consent withdrawal.

• Up to 120 patients will be accrued to the study. It is anticipated that 20-30 patients per year may enroll into this trial; thus accrual may be completed in 4-5 years. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Neuroendocrine
• Neoplasms
• Neuroendocrine Carcinoma
• Neuroendocrine Neoplasms
• Neuroendocrine Tumors
• Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas

• NCT number: NCT02315625
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: April 8, 2015
• Completion date: May 22, 2019