Efficacy of Rechallenge With Sunitinib in Metastatic Pancreatic Neuroendocrine Tumor Previously Failed to Sunitinib

NCT02713763 | Completed Phase 2

• 2 other identifiers: GETNE-2016-012015-005774-37
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 9

Brief Summary

The therapeutic goals in the management of pancreatic neuroendocrine tumors (pNET) are the control of symptoms and tumor growth control in order to improve patient survival. In recent years, data from two phase III studies with targeted therapies, sunitinib and everolimus, have broadened the possibilities for treatment of patients with neuroendocrine tumors of the pancreas. Unfortunately, patients progress and development of new active drugs and evaluating the best treatment approach is decisive. Given the lack of data comparing the activity of different treatment strategies, final decisions are based on medical experience and consensus of experts. In this context, different questions are still unanswered, as which is the best sequence of treatment and if all patients can benefit from all available drugs. Neuroendocrine pancreatic tumors are highly vascularized tumors in which cells may be dependent on this pathway for growth throughout the entire history of the tumor and in which inhibition of this pathway is crucial. On the other hand, this aspect has not been endorsed by the population of patients with pNET who have previously failed treatment with sunitinib. In this scenario the investigators will assess retreatment with sunitinib to evaluate the activity of this drug in the context of therapeutic rescue in patients with metastatic pNET.

Conditions

Pancreatic Neuroendocrine Tumour Metastatic

Keywords

Sunitinib

Outcome Measures

Primary Outcomes (1)

• 6 months progression free survival

  Time form start of treatment to progression disease

  6 months

Secondary Outcomes (5)

• Overall survival

  2 years

• Progression free survival

  12 months

• Response duration

  12 months

• Overall response rate

  12 months

• Incidence of Adverse Events

  12 months

Study Arms (1)

Sunitinib

EXPERIMENTAL

Sunitinib 37.5 mg/day

Drug: Sunitinib

Interventions

Sunitinib DRUG

Sunitinib 37.5 mg/day

Also known as: Sutent

Sunitinib

Eligibility Criteria

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

You may qualify if:

• Subjects \> 18 years old and able to give their informed consent.
• Patients diagnosed with Neuroendocrine Tumor of pancreatic origin and histologically confirmed, G1/2 according to the World Health Organization (WHO) classification (Ki67 \<20% and/or mitotic count \>20 mitoses x 10 HPF).
• Metastatic disease progression in the 12 months prior to baseline visit documented by CT, MRI or Octreoscan.
• Progression to prior treatment with sunitinib administered for metastatic disease and have received at least 1 line and no more than 2 lines of subsequent systemic treatment.
• Measurable disease according to the following criteria RECIST version 1.1
• No disease that can be treated with surgery, radiotherapy or combined treatment with curative intent.
• Eastern Cooperative Oncology Group (ECOG) 0-2.
• Pretreatment with somatostatin analogues, chemotherapy, anti-VEGF (vascular endothelial growth factor) and mTOR (mammalian target of rapamycin) inhibitors prior to participation in the study is allowed.
• Adequately controlled blood pressure (BP) \<150/90 mmHg.
• Hematologic Function: - Absolute neutrophil count \>1500 / microliter (uL) - Platelets \>100,000 / uL - Hemoglobin \>5.6 mmol / L (9 g / dL)
• Liver function: total bilirubin \< 1.5 x upper limit of normal (ULN), unless unconjugated hyperbilirubinemia or Gilbert syndrome. - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5 x ULN (\< 5 times in case of liver metastases).
• Renal function: calculated creatinine clearance according to Cockcroft-Gault \> 30 ml / min.
• Blood coagulation: prothrombin time (PT) or International Normalized Ratio (INR) \< 1.2 x ULN.
• Proteinuria \<2+ urine dipstick. If \> 2+ proteinuria, urinary protein \<1 g / 24 h.
• Life expectancy\> 3 months.

You may not qualify if:

• Neuroendocrine tumors of pancreatic origin G3 according to WHO classification.
• Patients who received 3 or more lines of systemic treatment.
• Major surgery or trauma within 4 weeks prior to the first dose of sunitinib.
• Radiation therapy or tumor embolization within 2 weeks prior to the first dose of sunitinib.
• Chemotherapy, immunotherapy, biologic therapy or investigational therapy within the previous 2 weeks or 5 half-lives of the drug last received before the start of the first dose of sunitinib treatment.
• Prior treatment with high-dose chemotherapy that required hematopoietic rescue.
• Immunosuppressive therapy or prolonged treatment with corticosteroids concomitantly administered in the previous 3 months.
• Resolution to grade \<2 (CTCAE according V4.03) of all previous related toxicities except alopecia treatments.
• Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 (according CTCAE V4.03) and/or that is progressing in severity, except alopecia.
• Treatment with potent inhibitors or inducers of CYP3A4 or known to prolong the QT interval in the previous 7 days.
• Prior radiotherapy to more than 25% of the bone marrow - Presence of uncontrolled metastatic brain disease, spinal cord compression, meningeal carcinomatosis or leptomeningeal disease.
• Any gastrointestinal malabsorption disorder or any other condition that, at investigator's criteria, may affect the absorption of sunitinib or increase the risk of bleeding or perforation.
• Presence of any non-healing wound or ulcer.
• Grade III/IV diarrhea in the screening period.
• Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead
• Pfizer: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (9)

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Universitario Valle de Hebrón

Barcelona, 08035, Spain

Location

Hospital Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario Donostia

Donostia / San Sebastian, 20014, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital General Universitario J.M. Morales Meseguer

Murcia, 30008, Spain

Location

Complejo Hospitalario Regional Virgen Del Rocío

Seville, 41013, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

MeSH Terms

Interventions

Sunitinib

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Enrique Grande

  MD Anderson Cancer Center MADRID

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 21, 2016
• Study Start: February 14, 2017
• Primary Completion: October 23, 2019
• Study Completion: October 23, 2019
• Last Updated: March 4, 2020

Record last verified: 2020-03

Locations

ES (9)