Platinum-doublet Chemotherapy and Nivolumab for the Treatment of Subjects With Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin.

NCT03980925 | Completed Phase 2 Results DMC

• 1 other identifier: GETNE-T1913
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 12

Brief Summary

This is a prospective, multi-centre, open label, non-randomized phase II study evaluating the efficacy and safety of nivolumab plus platinum-based chemotherapy in patients with advanced G3 NENs of the GEP tract or of UK origin.

Conditions

Neuroendocrine Tumors; Neuroendocrine Neoplasm; Gastroenteropancreatic Neuroendocrine Tumor

Outcome Measures

Primary Outcomes (1)

• Overall Survival Rate at 12 Months

  Percentage of patients alive at 1-year from first dose of treatment.

  12 months

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Throughout the study period, approximately 24 months

• Progression-free Survival (PFS) Rate

  Throughout the study period, approximately 24 months

• Median Overall Survival

  30 months

• Predictive Biomarkers

  30 months

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  30 months

Study Arms (1)

Nivolumab + platinum-doublet chemotherapy

EXPERIMENTAL

1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until progression of the disease (PD), death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.

Drug: Nivolumab; Drug: Carboplatin; Drug: Etoposide

Interventions

Nivolumab DRUG

Subjects will receive Nivolumab 360 mg every 3 weeks (Q3W) first day of each cycle plus Carboplatin area under the curve (AUC5) Q3W first day of each cycle plus Etoposide 100 day 1-3 of each cycle up to 6 cycles of combined therapy (Induction Phase). At the time of completion of 6 cycles of chemotherapy and nivolumab, participants who have not experienced disease progression will continue to receive nivolumab at a dose of 480 mg as 30 minute infusion every 4 weeks for up to 2 years (24 months) (maintenance phase). Cycles are defined by 4 weeks or 28 days.

Nivolumab + platinum-doublet chemotherapy

Carboplatin DRUG

Subjects will receive Nivolumab 360 mg every 3 weeks (Q3W) first day of each cycle plus Carboplatin AUC5 Q3W first day of each cycle plus Etoposide 100 day 1-3 of each cycle up to 6 cycles of combined therapy (Induction Phase). At the time of completion of 6 cycles of chemotherapy and nivolumab, participants who have not experienced disease progression will continue to receive nivolumab at a dose of 480 mg as 30 minute infusion every 4 weeks for up to 2 years (24 months) (maintenance phase). Cycles are defined by 4 weeks or 28 days.

Nivolumab + platinum-doublet chemotherapy

Etoposide DRUG

Subjects will receive Nivolumab 360 mg every 3 weeks (Q3W) first day of each cycle plus Carboplatin AUC5 Q3W first day of each cycle plus Etoposide 100 day 1-3 of each cycle up to 6 cycles of combined therapy (Induction Phase). At the time of completion of 6 cycles of chemotherapy and nivolumab, participants who have not experienced disease progression will continue to receive nivolumab at a dose of 480 mg as 30 minute infusion every 4 weeks for up to 2 years (24 months) (maintenance phase). Cycles are defined by 4 weeks or 28 days.

Nivolumab + platinum-doublet chemotherapy

Eligibility Criteria

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

You may qualify if:

• Confirmed G3 NENs originated in the gastroenteropancreatic tract (WHO 2010 classification). Patients with a G3 NEN of unknown primary will also be eligible for this trial.
• Ki-67 \>20% or mitotic rate \> 20 per 10 High-power field (HPF).
• Metastatic or locally advanced unresectable disease not amenable to treatment with curative intent.
• No prior systemic treatment for advanced disease nor as adjuvant therapy.
• Availability of fresh or archive formalin-fixed, paraffin-embedded tumor tissue for biomarker assessment.
• Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable as per RECIST 1.1.
• Adequate organ function as defined by the following criteria (within 7 days prior to enrollment):
• absolute neutrophil count (ANC) ≥1500 cells/mm3
• platelets ≥100,000 cells/mm3
• hemoglobin ≥9.0 g/dL
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); in patients with liver metastases AST and ALT ≤5.0 x ULN
• total bilirubin ≤1.5 x ULN
• serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min.
• Male or female, age ≥18 years.
• Eastern cooperative oncology group (ECOG) performance status of 0-2.

You may not qualify if:

• The following endocrine tumor types may not be included: paraganglioma, adrenal, thyroid parathyroid or pituitary endocrine tumors. Large or small cell lung neuroendocrine carcinoma of the lung will also be excluded.
• Prior therapy with any immune checkpoint inhibitor.
• Major surgery, except diagnostic biopsy, in \<4 weeks or radiation therapy \<2 weeks prior to starting study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
• Prior organ transplantation, including allogeneic stem-cell transplantation.
• Prior history of non-infectious pneumonitis requiring steroids or current pneumonitis.
• Systemic chronic steroid therapy (\> 10 mg/day prednisone or equivalent) or other immunosuppressive agents or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of steroids for allergic reactions or management of immune-related adverse events is allowed. Topical, inhaled, nasal and ophthalmic steroids are also allowed.
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
• Known history of positive testing for Human Immunodeficiency Virus (HIV) infection, known history of or positive tests for Hepatitis B virus surface antigen (HBVsAg) or Hepatitis C ribonucleic acid (HCV RNA) indicating acute or chronic infection or other significant acute or chronic infections requiring medication at study entry.
• Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease. (Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll).
• Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
• A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment will not be allowed to enter the study. Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, new york heart association (NYHA) class \> III congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
• Known hypersensitivity reactions to monoclonal antibodies (≥ grade 3 according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 \[xliii\] or any past medical history of anaphylaxis or uncontrolled asthma (i.e., 3 or more asthma characteristics partially controlled).
• Any other prior malignancy within 5 years of study entry, with the exception of adequately treated in-situ carcinoma of the cervix, breast or uteri, or non-melanomatous skin cancer.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead

Study Sites (12)

Institut Català d'Oncologia Badalona

Badalona, Barcelona, Spain

Location

Institut Català d'Oncologia l'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Vall d'Hebron University Hospital

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

MD Anderson Cancer Madrid

Madrid, Spain

Location

Hospital Clínico Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Gastro-enteropancreatic neuroendocrine tumor

Interventions

Nivolumab; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Federico Nepote
• Organization: MFAR Clinical Research

investigacion@mfar.net

+34 93 434 44 12

Study Officials

• Rocío García-Carbonero, MD, PhD

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

• Maria del Carmen Riesco-Martínez, MD, PhD

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: June 7, 2019
• First Posted: June 10, 2019
• Study Start: October 11, 2019
• Primary Completion: February 13, 2023
• Study Completion: June 9, 2023
• Last Updated: January 13, 2025
• Results First Posted: January 13, 2025

Record last verified: 2024-11

Locations

ES (12)