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
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|ClinicalTrials.gov Identifier: NCT02315625|
Recruitment Status : Recruiting
First Posted : December 12, 2014
Last Update Posted : June 19, 2018
- 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.
- To see if drugs selected based on the defective gene result in better tumor response. The drugs are sunitinib and everolimus.
- People age 18 and older with an advanced low- or intermediate-grade gastrointestinal or pancreatic neuroendocrine tumor.
- Participants will be screened with:
<TAB>- Medical history
<TAB>- Physical exam
<TAB>- Blood, urine, and lab tests
- The study team will see if participants should have surgery.
- If yes, participants will:
- Sign a separate consent
- Have 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.
|Condition or disease||Intervention/treatment||Phase|
|Neuroendocrine Tumors||Drug: Sunitinib Drug: Everolimus||Phase 2|
- 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 CDKN1B, and genes involved in the PI3K/AKT/mTOR signaling pathway, and/or overexpression of growth factors and their receptors such as VEGF, VEGFR, PDGF, and 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.
-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.
- progressive, histologically or cytologically diagnosed low or intermediate grade locally advanced or metastatic NETs.
- Age greater than or equal to 18 years
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||March 24, 2015|
|Estimated Primary Completion Date :||September 7, 2020|
|Estimated Study Completion Date :||September 6, 2021|
Experimental: Arm 1
37.5 mg once daily will continue until progression
Experimental: Arm 2
10 mg daily
4 x 2.5 mg tablets
- Progression Free Survival (PFS) [ Time Frame: at progression ]Median amount of time subject survives without disease progression after treatment
- overall response rate (ORR) [ Time Frame: Every 3 months until disease progression ]Proportion of patients whose tumors shrunk after therapy
- overall survival and median survival time (MST) [ Time Frame: Death ]Median amount of time subject survives after therapy
- realationship between tumor genotype, treatment and PFS [ Time Frame: 4 years ]Correlation between tumor genotype, treatment and PFS
- Safety endpoints [ Time Frame: 30 days after treatment discontinuation ]List of adverse event frequency
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02315625
|Contact: Cara M Kenney, R.N.||(240) email@example.com|
|Contact: Dhaval T Patel, M.D.||(301) firstname.lastname@example.org|
|United States, Illinois|
|Rush University Medical Center||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Xavier Keutgen, MD 312-563-1557 email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Dhaval T Patel, M.D.||National Cancer Institute (NCI)|