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Neuroendocrine TumorsPhase 2/3NCT01744249

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

A Phase 2/3 study testing Axitinib and Sandostatin LAR in people with Neuroendocrine Tumors and Advanced Cancer, run by Grupo Espanol de Tumores Neuroendocrinos at 26 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Tumors, Advanced Cancer
What is being tested?
Axitinib and Sandostatin LAR
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
256 participants
Where
26 sitesin 4 countries
Study dates
Nov 2011to 31 Dec 2023
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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,
  • Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min,
  • Proteinuria < 2+ by reactive strip. If the reactive strip is ≥ 2+, a 24-hour urine sample should be collected and the patient may be eligible if urinary protein excretion is < 2 g every 24 hours.
  • Men or women aged ≥ 18 years.
  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • At least 4 weeks should pass from the end of the previous systemic treatment with resolution of all treatment-related toxicities to grade ≤ 1 according to NCI CTCAE Version 4.0 or to baseline, except for alopecia or properly treated hypothyroidism.
  • No prior evidence of uncontrolled hypertension should exist, as documented by 2 baseline blood pressure readings taken at least 1 hour apart. Baseline readings of systolic blood pressure should be ≤ 150 mm Hg and baseline readings of diastolic pressure should be ≤ 90 mm Hg. Patients whose hypertension is being controlled with antihypertensive therapy are eligible.
  • Women (or their partners) should be surgically sterilized or postmenopausal, or must agree to use an effective contraceptive method during and for at least 6 months after receiving study treatment. All women of childbearing age should have a negative pregnancy test (serum/urine) within 7 days prior to starting treatment. Men (or their partners) should be surgically sterilized or must agree to use an effective contraceptive method during and for at least 6 months after receiving study treatment. The definition of an effective contraceptive method must comply with local regulations and will be based on the criterion of the principal investigator or a designated associate. Lactating women may not participate in this study.
  • Signed and dated informed consent document stating that the patient has been informed of all the pertinent aspects of the trial prior to recruitment.
  • Willingness and ability to comply with scheduled visits, treatment plans (including willingness to take axitinib or placebo according to randomization), laboratory tests, and other study procedures.

Who cannot join

  • 1. Subjects must be evaluated with regard to the following exclusion criteria:
  • 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;
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  • 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.
  • Any of the following events in the 12 months prior to administration of the study drug: myocardial infarction, uncontrolled angina, implantation of a coronary or peripheral bypass, symptomatic congestive heart failure, stroke or transient ischemic attack. Deep vein thrombosis or pulmonary embolism in the prior 6 months.
  • Ongoing grade ≥ 2 cardiac arrhythmias according to NCI CTCAE: atrial fibrillation of any grade or QTc interval > 450 ms for men or > 470 ms for women.
  • Patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related disease.
  • Prior history of cancer except those treated with curative intent for non-melanoma skin cancer in situ, breast or cervical cancer in situ, or those treated for any cancer with curative intent and no evidence of disease in the last 5 years prior to enrollment in the study.
  • Dementia or significantly altered mental status that could prevent compression, or submission of informed consent and compliance with the requirements of this protocol.
  • Any severe, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with participation in the study or with study drug administration, or that may interfere with the interpretation of results, and that could interfere with the patient's ability to take part in this study in the investigator's opinion.
  • The patient's participation or intention to participate (in the 4 weeks prior to starting drug administration) in a study in which the patient will receive an investigational medicinal product.
  • Subjects who are institutionalized by governmental or by judicial decision, or subjects who are dependent of the sponsor, the investigator or the trial site will be excluded from participation.

Trial locations and contacts

26 sites in 4 countries.

26 sites in 4 countries

Spain22 sites

  • Complejo Hospitalario Univ A Coruña

    A Coruña

  • Hospital Universitari Vall d'Hebron

    Barcelona

  • Hospital Universitario de Burgos

    Burgos

  • Hospital de Donostia

    Donostia / San Sebastian

  • Hospital Virgen de las Nieves

    Granada

  • Institut Català d'Oncologia L'Hospitalet

    L'Hospitalet de Llobregat, Barcelona

  • Hospital universitario de Leon

    León

  • MD Anderson Cancer Center

    Madrid, 28033

  • Hospital Clara Campal

    Madrid

  • Hospital Clínico San Carlos

    Madrid

  • Hospital Gregorio Marañón

    Madrid

  • Hospital Univ La Paz

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario Ramón y Cajal

    Madrid

  • Hospital Universitario Virgen de la Victoria

    Málaga, Malaga, 29010

  • Hospital Central de Asturias

    Oviedo, Principality of Asturias

  • Hospital Univ de Salamanca

    Salamanca

  • Hospital Marqués de Valdecilla

    Santander

  • Hospital Universitario Virgen del Rocío

    Seville

  • Hospital General Universitario de Valencia

    Valencia, 46014

  • Hospital Alvaro Cunqueiro

    Vigo, Pontevedra, 36312

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

Italy2 sites

  • Azienda Ospedaliera Universitaria di Perugia

    Perugia, 06129

  • Sapienza, Universitá di Roma, Ospedale sant'Andrea

    Rome, 00189

Other trials in Italy

Germany1 site

  • Marburg Universitätsklinikum Giessen und Marburg GmbH

    Marburg, 35043

Other trials in Germany

United Kingdom1 site

  • Clatterbridge Cancer Centre

    Bebington, Wirral, CH63 4JY

Other trials in United Kingdom

About this study

Official title: A Phase II/III Randomized Double-blind Study of Sandostatin LAR in Combination With Axitinib Versus Sandostatin LAR With Placebo in Patients With Advanced G1-G2 Neuroendocrine Tumours (WHO 2010) of Non-pancreatic Origin

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.

Read the detailed description

Phase II/III, prospective, multicenter, randomized (1:1), double-blind study to evaluate the efficacy and tolerability of axitinib in patients diagnosed with advanced G1-G2 neuroendocrine tumors (WHO 2010) of nonpancreatic origin that have presented documented disease progression in the 12 months prior to entering the study. In the first part of the study (Phase II), 105 patients were enrolled. The second part of the study is the expansion to Phase III, which is expected to include 148 additional patients. Patients will be randomized to receive Sandostatin LAR with axitinib or Sandostatin LAR with placebo until disease progression or unacceptable toxicity occurs. Randomization will be stratified by the time from diagnosis to enrollment in the study (more vs less than or equal to 12 months), the origin of the primary tumor (gastrointestinal tract vs non-gastrointestinal tract [lung or other sites]) and ki-67 (< 5% vs > 5%).

Being tested
Axitinib, Sandostatin LAR, Placebo
Keywords
Advanced neuroendocrine tumours of non-pancreatic origin, axitinib
Medical subject headings
Neuroendocrine Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AxitinibDrug

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

  • Sandostatin LARDrug

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

  • PlaceboDrug

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

Study groups in NCT01744249
Study groupRoleWhat they receive
Axitinib + Sandostatin LARExperimentalAxitinib 5 mg BID + Sandostatin LAR 30mg/28 days
Receives: Drug: Axitinib; Drug: Sandostatin LAR
Placebo + Sandostatin LARPlacebo comparatorPlacebo BID + Sandostatin LAR 30mg/28 days
Receives: Drug: Sandostatin LAR; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

  1. Objective Response Rate (ORR) (Investigator Assessment)

    Measured changes in the sum of longest diameter of target lesions measured in mm according to RECIST 1.1 criteria. Assessed by investigators.

    Patients are categorized depending on the percentage of tumor redution:

    Complete response (CR): dissapearance of all lesions Partial response (PR): reduction > 30% in the sum of longest diameter of target lesions Stable disease (SD): Tumor size betwee 30% reduction and 20% increase in the sum of longest diameter of target lesions Progressive disease (PD): increase > 20% in the sum of longest diameter of target lesions

    ORR comprise all patients who achieved at least a CR or PR at any timepoint during follow-up.

    Measured: 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

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

    measurable in mL/ 24h and ng/ml respectively, through blood and urine test in patients with baseline elevation of CgA or 5-HIAA levels. This endpoint measures the negativization of these two tumor biomarkers.

    Measured: 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

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

    All adverse events and serious adverse events will be monitored with regular monitoring of hematology and blood chemistry parameters and regular physical examinations. Adverse events will be evaluated continuously throughout the study. Safety and tolerability will be assessed according to the National Institute of Health/National Cancer Institute (NIH/NCI) Common Terminology Criteria for Adverse Events version 4 (CTCAE v4)

    Measured: 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

  4. Efficacy of Axitinib in Terms of PFS (Central Blinded 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 central blinded reviewers using tumor imaging by 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

    Measured: 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

  5. Objective Response Rate (ORR) (Central Blinded Assessment)

    Measured changes in the sum of longest diameter of target lesions measured in mm according to RECIST 1.1 criteria. Assessed by central blinded reviewers.

    Patients are categorized depending on the percentage of tumor redution:

    Complete response (CR): dissapearance of all lesions Partial response (PR): reduction > 30% in the sum of longest diameter of target lesions Stable disease (SD): Tumor size betwee 30% reduction and 20% increase in the sum of longest diameter of target lesions Progressive disease (PD): increase > 20% in the sum of longest diameter of target lesions

    ORR comprise all patients who achieved at least a CR or PR at any timepoint during follow-up.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2012 (estimated)
  2. Study startNov 2011
  3. Primary completion31 Dec 2023
  4. Study completion31 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
256 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01744249
Sponsor's protocol ID
AXI-IIG-02
Other IDs
2011-001550-29
Status last verified
Apr 2026
First submitted
25 Sep 2012
Last updated
28 Apr 2026
Data monitoring committee
No

Publications

  • 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.

    PubMed 41719493

  • 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.

    PubMed 33152282

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Axitinib and Sandostatin LAR in people with Neuroendocrine Tumors and Advanced Cancer, run by Grupo Espanol de Tumores Neuroendocrinos at 26 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Spain, Italy, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of Axitinib in Terms of PFS (Investigator Assessment) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01744249, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.

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