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

NCT02402062 | Completed Phase 2 Results DMC

• 2 other identifiers: GETNE-14082014-004072-30
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Neuroendocrine Tumors; Pancreatic Neoplasms

Keywords

pNET

Outcome Measures

Primary Outcomes (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

  approximately 36 months

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  approximately 36 months

• Time to Tumour Progression (TTP)

  approximately 36 months

• Duration of Response (DR)

  approximately 36 months

• Overall Survival (OR)

  approximately 36 months

• Safety (Adverse Events)

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

Study Arms (1)

TH-302 + Sunitinib

EXPERIMENTAL

TH-302 + Sunitinib. Single arm Study.

Drug: TH-302 + Sunitinib

Interventions

TH-302 + Sunitinib DRUG

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.

Also known as: TH-302 + Sutent

TH-302 + Sunitinib

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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 %

Sponsors & Collaborators

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

Study Sites (10)

Institut Catalá d'Oncologia L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Provincial de Castellón

Castellon, Valencia, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Related Publications (1)

• 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.

  PMID: 34190375 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive

Interventions

TH 302; Sunitinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Federico Nepote
• Organization: MFAR Clinical Research

investigacion@mfar.net

0034934344412

Study Officials

• Enrique Grande, MD

  Grupo Espanol de Tumores Neuroendocrinos

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: February 26, 2015
• First Posted: March 30, 2015
• Study Start: May 11, 2015
• Primary Completion: May 31, 2018
• Study Completion: January 10, 2020
• Last Updated: July 27, 2020
• Results First Posted: July 27, 2020

Record last verified: 2020-07

Locations

ES (10)