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Neuroendocrine TumorsPhase 2NCT02402062

A Study to Assess the Safety and the Efficacy of the Combination of TH-302 and Sunitinib in Neuroendocrine Pancreatic Tumours

A Phase 2 study testing TH-302 + Sunitinib in people with Neuroendocrine Tumors and Pancreatic Neoplasms, run by Grupo Espanol de Tumores Neuroendocrinos at 10 sites in Spain.

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

The purpose of this study is to determine the safety and the efficacy of the combination of the drugs TH-302 and sunitinib in metastatic neuroendocrine tumours. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Tumors, Pancreatic Neoplasms
What is being tested?
TH-302 + Sunitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
10 sitesSpain
Study dates
11 May 2015to 10 Jan 2020
Phase
Phase 2
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

  • Male or female, 18 years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Histologically proven diagnosis of pancreatic neuroendocrine tumors (pNET) with Ki67 assessment of ≤ 20% (well and moderately differentiated)
  • Evidence of unresectable disease or metastatic disease. Locally advanced disease must not be amendable to resection or radiation therapy with curative intent.
  • Patients may be treated with somatostatin analogues prior or during the trial. Concomitant or prior interferon treatment is not permitted.
  • Documented progression disease by CT scan, magnetic resonance (MR) or Octreoscan in 12 months prior basal visit.
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  • Measurable disease as per RECIST. Measurable lesions that have been previously radiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy.
  • Patient has to be able to swallow the medication.
  • Life expectancy greater than 12 weeks.
  • The definitions of minimum adequacy for organ function required prior to study entry are as follows:
  • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
  • Total serum bilirubin ≤ 1.5 x ULN
  • Serum albumin ≥ 3.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1500/µL
  • Platelets ≥ 100,000/µL
  • Hemoglobin ≥ 5,6 mmol/L (9.0 g/dL)
  • Creatinin clearance > 40 mL/min (Cockcroft and Gault formula)
  • Adequate cardiac function: 12-lead ECG without pathologic findings (clinically significant alterations are allowed) and Echocardiogram / Normal multiple gated acquisition scan (MUGA) (LVEF> 50%)
  • Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Who cannot join

  • Previous treatments with chemotherapy, monoclonal antibodies anti-vascular endothelial growth factor (VEGF), tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, or interferon are not permitted for the advanced disease.
  • Prior treatment on another hypoxia-activated prodrug under clinical trial.
  • Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization except palliative radiotherapy to non-target metastatic lesions.
  • Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
  • Immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken concurrently or within last 3 months prior to randomization
  • Treatment with known inhibitors or inductors of cytochrome P450 3A4 (CYP3A4) or that prolong the QT interval in the previous 7 days.
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  • Prior radiation therapy to > 25% of the bone marrow.
  • Current treatment on another clinical trial.
  • Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients should have completed surgery or radiation therapy for existing brain metastases, should not have documented increase in size over the previous 3 months prior to first dose of treatment on study and should be asymptomatic.
  • Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
  • Any of the following within the 12 months prior to starting study treatment:
  • myocardial infarction,
  • severe/unstable angina,
  • coronary/peripheral artery bypass graft,
  • congestive heart failure class III or IV of the New York Heart Association (NYHA) or patients with clinical history of congestive heart failure class III or IV of the NYHA, unless an echocardiogram or MUGA in the previous 3 months to selection shows a LVEF ? 45 %
  • significant heart valve disease
  • cerebrovascular accident including transient ischemic attack
  • pulmonary embolus.
  • Ongoing cardiac dysrhythmias of NCI Common Toxicity Criteria for Adverse Effects (CTCAE) grade ≥ 2, atrial fibrillation of any grade, or corrected QT interval (QTc) interval >450 msec for males or >470 msec for females.
  • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
  • Chronic obstructive pulmonary disease (COPD) or any other disease concurrent with hypoxemia or oxygen saturation < 90% after a march of two minutes.
  • Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
  • Known human immunodeficiency virus infection.
  • Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to inclusion.
  • Previous allergic reaction to components structurally similar to TH-302 or sunitinib or any of the excipients of drugs.
  • Non-healing wound, fistulae, active peptic ulcer or bone fracture.
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Provincial de Castellón

    Castellon, Valencia

  • Hospital Universitario Virgen de las Nieves

    Granada, 18014

  • Institut Catalá d'Oncologia L'Hospitalet

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Universitario Marqués de Valdecilla

    Santander, Cantabria, 39008

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

Other trials in Spain

About this study

Official title: A Phase II Study to Assess the Activity and Safety of TH-302 in Combination With Sunitinib in Treatment-naïve Patients With Well- and Moderately-differentiated Metastatic Pancreatic Neuroendocrine Tumours (pNET)

The purpose of this study is to determine the safety and the efficacy of the combination of the drugs TH-302 and sunitinib in metastatic neuroendocrine tumours.

Read the detailed description

The purpose of this study is to determine the safety and the efficacy of the combination of the drugs TH-302 and sunitinib in Treatment-naïve patients with well- and moderately-differentiated metastatic Pancreatic Neuroendocrine Tumours (pNET).

Being tested
TH-302 + Sunitinib
Keywords
pNET
Medical subject headings
Neuroendocrine Tumors, Pancreatic Neoplasms, Neuroectodermal Tumors, Primitive

What participants receive

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

  • TH-302 + SunitinibDrug

    Also called TH-302 + Sutent

    Combination of the two drugs in cycles of 28 days, described as follows:

    Sunitinib: 37,5 mg/day Oral everyday of each 28 day cycle.

    TH-302: 340 mg/m2 IV on days 8, 15 and 22 of each cycle.

Study groups in NCT02402062
Study groupRoleWhat they receive
TH-302 + SunitinibExperimentalTH-302 + Sunitinib. Single arm Study.
Receives: Drug: TH-302 + Sunitinib

What is being measured

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

  1. Objective Response Rate

    Objective response rate: percentage of patients in whom a complete response (CR) or a partial response (PR) is confirmed according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in relation to the total of the analyzed population.

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions

    Measured: approximately 36 months

Secondary outcomes (6)

  1. Progression Free Survival (PFS)

    Time between the start of study treatment to date of the first objective evidence of radiological progression or patient death due to any cause; which comes first.

    Measured: approximately 36 months

  2. Time to Tumour Progression (TTP)

    It is defined as the time between the start of study treatment to date of the first objective evidence of radiological progression.

    Measured: approximately 36 months

  3. Duration of Response (DR)

    It is defined as the time between the start from the first documentation of objective response (CR or PR) which is subsequently confirmed until the first objective evidence of radiological progression or death from any cause. DR is calculated only in the subgroup of patients with an objective response (CR + PR).

    Measured: approximately 36 months

  4. Overall Survival (OR)

    It is defined as the time between the start of study treatment to date of death from any cause. If it were impossible to obtain confirmation of the death, survival will be censored with the date of the last Visit that it is satisfied that the patient was alive.

    Measured: approximately 36 months

  5. Safety (Adverse Events)

    Safety will be assessed according to the reports of adverse events, the frequency of treatment discontinuations due to adverse events, laboratory evaluations or ECG

    Measured: time between the date of signing the informed consent until 28 days after the last dose of study drug, , an average of 2 years

  6. Biomarkers in Serum and Tumor Tissue

    Assess the predictive/prognostic value of the analysed biomarkers in plasm and tumour.

    Measured: approximately 36 months

Timeline

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

  1. First posted30 Mar 2015 (estimated)
  2. Study start11 May 2015
  3. Primary completion31 May 2018
  4. Study completion10 Jan 2020

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02402062
Sponsor's protocol ID
GETNE-1408
Other IDs
2014-004072-30, 2014
Status last verified
Jul 2020
First submitted
26 Feb 2015
Last updated
27 Jul 2020
Data monitoring committee
Yes

Publications

  • Grande E, Rodriguez-Antona C, Lopez C, Alonso-Gordoa T, Benavent M, Capdevila J, Teule A, Custodio A, Sevilla I, Hernando J, Gajate P, Molina-Cerrillo J, Diez JJ, Santos M, Lanillos J, Garcia-Carbonero R. Sunitinib and Evofosfamide (TH-302) in Systemic Treatment-Naive Patients with Grade 1/2 Metastatic Pancreatic Neuroendocrine Tumors: The GETNE-1408 Trial. Oncologist. 2021 Nov;26(11):941-949. doi: 10.1002/onco.13885. Epub 2021 Jul 14.

    PubMed 34190375

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TH-302 + Sunitinib in people with Neuroendocrine Tumors and Pancreatic Neoplasms, run by Grupo Espanol de Tumores Neuroendocrinos at 10 sites in Spain.

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 20 inclusion and 27 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 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Spain. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this 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.

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 27 Jul 2020). 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?

Objective Response Rate (time frame: approximately 36 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 NCT02402062, which also lists 1 linked publication.

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 27 Jul 2020.

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