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

NCT ID: NCT02402062

Last Updated: 2020-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-11
• Study Completion Date: 2020-01-10

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.

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).

Conditions

Neuroendocrine Tumors; Pancreatic Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TH-302 + Sunitinib

TH-302 + Sunitinib. Single arm Study.

Group Type: EXPERIMENTAL

TH-302 + Sunitinib

Intervention Type: 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.

Interventions

TH-302 + Sunitinib

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.

Intervention Type: DRUG

Other Intervention Names

TH-302 + Sutent

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

Exclusion Criteria

• 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 %
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Threshold Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

Grupo Espanol de Tumores Neuroendocrinos

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enrique Grande, MD

Role: STUDY_CHAIR

Grupo Espanol de Tumores Neuroendocrinos

Locations

Institut Catalá d'Oncologia L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Hospital Provincial de Castellón

Castellon, Valencia, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 34190375 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-004072-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GETNE-1408

Identifier Type: -

Identifier Source: org_study_id