Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas

NCT01744249 | Completed Phase 2 Results

• 2 other identifiers: AXI-IIG-022011-001550-29
• Study Type: interventional
• Target: 256
• Locations: 4 countries
• Sites: 26

Brief Summary

Assess whether therapy with axitinib, a potent angiogenic inhibitor of the tyrosine kinase receptors of VEGF bioavailable by oral administration, is capable of improving PFS in patients with advanced G1-G2 NETs of nonpancreatic origin with progressive disease documented in the 12 months prior to entering the study.

Conditions

Neuroendocrine Tumors; Advanced Cancer

Keywords

Advanced neuroendocrine tumours of non-pancreatic origin; axitinib

Outcome Measures

Primary Outcomes (1)

• Efficacy of Axitinib in Terms of PFS (Investigator Assessment)

  Calculated from the date of random assignment until the date of first progressive disease or death, whichever occurs first. Progression of the disease was assessed by investigators using tumor imaging computed tomography scans and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 PFS was analysed by Kaplan-Meier method and compared with log-rank tests. Patients alive with no event at data cut off were censored on their last tumor assessment

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months

Secondary Outcomes (5)

• Objective Response Rate (ORR) (Investigator Assessment)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months

• Biochemical Response (5-OH-indoleacetic Acid and Chromogranin A)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months

• Safety and Tolerability of Axitinib (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE], Version 4.0)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months

• Efficacy of Axitinib in Terms of PFS (Central Blinded Assessment)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months

• Objective Response Rate (ORR) (Central Blinded Assessment)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 25 months

Study Arms (2)

Axitinib + Sandostatin LAR

EXPERIMENTAL

Axitinib 5 mg BID + Sandostatin LAR 30mg/28 days

Drug: Axitinib; Drug: Sandostatin LAR

Placebo + Sandostatin LAR

PLACEBO COMPARATOR

Placebo BID + Sandostatin LAR 30mg/28 days

Drug: Sandostatin LAR; Drug: Placebo

Interventions

Axitinib DRUG

Orally, 5mg, twice daily, until progression or until unacceptable toxicity, with or without food intake.

Axitinib + Sandostatin LAR

Sandostatin LAR DRUG

Intramuscular, 30mg, single injection every 28 days, until disease progression or unacceptable toxicity

Axitinib + Sandostatin LAR; Placebo + Sandostatin LAR

Placebo DRUG

orally, twice daily, until disease progression or unacceptable toxicity, with or without food intake.

Placebo + Sandostatin LAR

Eligibility Criteria

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

You may qualify if:

• G1-G2 neuroendocrine tumor (WHO 2010) of histologically confirmed non-pancreatic origin, functioning and nonfunctioning
• Metastatic or locally advanced disease not amenable to treatment with curative intent
• Clinical and/or radiological disease progression documented in the 12 months prior to study entry.
• Patients should have at least one measurable lesion as defined by RECIST 1.1 criteria. Patients should not have undergone local or regional ablative procedures (embolization, cryoablation, radiofrequency ablation, or others) in the 6 months prior to entering the study, unless there are other locations of measurable disease or clear radiological progression after carrying out these procedures (in these cases, local and regional ablation procedures shall be permitted if they have been performed at least 1 month prior to enrollment in the study).
• Ki-67 \< 20%
• Prior treatment with somatostatin analogues is allowed
• Prior treatment with interferon is allowed
• Prior treatment is allowed with up to 2 antineoplastic systemic treatment lines different from SAs or IFN (systemic treatment is understood as conventional cytotoxic chemotherapy or new drugs for therapeutic targets as mTOR or other, as long as it is not directed against VEGF/VEGFR). Treatment with SAs or IFN does not count as prior lines of antineoplastic treatment.
• Prior treatment with targeted therapy against VEGF or VEGFR is not allowed.
• Adequate organ function as defined by the following criteria:
• Absolute neutrophil count ≥ 1500 cells/mm3,
• Platelet count ≥ 75,000 cells/mm3,
• Hemoglobin ≥ 9.0 g/dL,
• AST y ALT ≤ 2.5 x upper limit of normal (ULN), except if liver metastases exist, in which case AST and ALT 5.0 ≤ x ULN is allowed,
• Total bilirubin ≤ 1.5 x ULN,

You may not qualify if:

• The following types of endocrine tumors will not be included: paraganglioma, adrenal endocrine tumor, thyroid, parathyroid, or pituitary.
• Major surgery within previous 4 weeks, or radiation therapy within 2 weeks prior to the start of treatment. Prior palliative radiotherapy for metastatic lesions is permitted if there is at least one measurable lesion that has not been irradiated (i.e., if there are other non-irradiated target lesions).
• Gastrointestinal abnormalities, including:
• Inability to swallow oral medication;
• Need for intravenous feeding;
• Prior surgical procedures that affect absorption, including total gastric resection;
• Treatment for active peptic ulcer in the last 6 months;
• Uncontrolled active gastrointestinal bleeding unrelated to cancer, as evidenced by hematemesis, hematochezia or clinically significant melena in the last 3 months without evidence of resolution documented by endoscopy or colonoscopy;
• Malabsorption syndromes;
• Current or anticipated need for treatment with drugs that are potent inhibitors of CYP3A4 (grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, and delavirdine) unless they can be replaced by another medication with minimal potential for CYP3A4/5 inhibition. The use of low-dose oral steroids (\< 5 mg/day prednisone or equivalent) is allowed. Co-administration of steroids may increase plasma concentrations of axitinib.
• Current use or anticipated need for treatment with drugs that are known potent CYP3A4/5 inducers (carbamazepine, dexamethasone, felbamate, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampicin, and St. John's wort) unless they can be replaced by another medication with minimal potential for CYP3A4 induction. Co-administration of CYP3A4/5 inducers may decrease plasma concentrations of axitinib.
• Need for anticoagulant therapy with oral vitamin K antagonists. Low doses of anticoagulants to maintain the patency of a central venous access device or to prevent deep vein thrombosis are permitted. Use with therapeutic doses of low molecular weight heparin is allowed.
• Clinically relevant history of bleeding in the last 6 months, including severe hemoptysis or hematuria, unless it has been due to a treated cause (e.g., completely resected bleeding intestinal tumor).
• Active epilepsy or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
• Serious uncontrolled illness or active infections that may interfere with the patient's ability to receive the study treatment.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead
• Pfizer: collaborator

Study Sites (26)

Marburg Universitätsklinikum Giessen und Marburg GmbH

Marburg, 35043, Germany

Location

Azienda Ospedaliera Universitaria di Perugia

Perugia, 06129, Italy

Location

Sapienza, Universitá di Roma, Ospedale sant'Andrea

Rome, 00189, Italy

Location

Institut Català d'Oncologia L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Malaga, 29010, Spain

Location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Hospital Central de Asturias

Oviedo, Principality of Asturias, Spain

Location

Complejo Hospitalario Univ A Coruña

A Coruña, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario de Burgos

Burgos, Spain

Location

Hospital de Donostia

Donostia / San Sebastian, Spain

Location

Hospital Virgen de las Nieves

Granada, Spain

Location

Hospital universitario de Leon

León, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Clara Campal

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Gregorio Marañón

Madrid, Spain

Location

Hospital Univ La Paz

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Univ de Salamanca

Salamanca, Spain

Location

Hospital Marqués de Valdecilla

Santander, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Clatterbridge Cancer Centre

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Related Publications (2)

• Garcia-Carbonero R, Benavent M, Jimenez-Fonseca P, Alonso-Gordoa T, Teule A, Custodio A, Tafuto S, La Casta A, Spada F, Lopez C, Ibrahim T, Iranzo V, Garcia-Alfonso P, Gonzalez-Flores E, Villanueva Silva MJ, Grande E, Panzuto F, Crespo G, Navarro M, Castellano D, Hernando J, Morales-Herrero R, Iglesias Alvarez G, Soldevilla B, Capdevila J. Axitinib and Long-Acting Octreotide in Advanced Extrapancreatic Neuroendocrine Tumors: A Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trial (AXINET, GETNE 1107). J Clin Oncol. 2026 Mar 20;44(9):774-786. doi: 10.1200/JCO-25-01808. Epub 2026 Feb 20.

  PMID: 41719493 DERIVED

• Kunz PL. Angiogenesis inhibitors in neuroendocrine tumours: finally coming of age. Lancet Oncol. 2020 Nov;21(11):1395-1397. doi: 10.1016/S1470-2045(20)30560-X. No abstract available.

  PMID: 33152282 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

Axitinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Secretary
• Organization: Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE)

getne@getne.org

0034934344412

Study Officials

• Rocio Garcia Carbonero, MD

  Hospital 12 de Octubre

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2012
• First Posted: December 6, 2012
• Study Start: November 1, 2011
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: April 28, 2026
• Results First Posted: April 28, 2026

Record last verified: 2026-04

Locations

GB (1); ES (22); DE (1); IT (2)