Clincosm LogoSign in Get a demo

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

Sponsor
Grupo Espanol de Tumores Neuroendocrinos (Other)
Overall Status
Completed
CT.gov ID
NCT02402062
Collaborator
Threshold Pharmaceuticals (Industry), Pfizer (Industry)
17
Enrollment
10
Locations
1
Arm
56
Actual Duration (Months)
1.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: TH-302 + Sunitinib
 Phase 2

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).

Study Design

Study Type:
Interventional
Actual Enrollment :
17 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
May 11, 2015
Actual Primary Completion Date :
May 31, 2018
Actual Study Completion Date :
Jan 10, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: TH-302 + Sunitinib

TH-302 + Sunitinib. Single arm Study.

Drug: 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.
Other Names:
  • TH-302 + Sutent

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate [approximately 36 months]

      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

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [approximately 36 months]

      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.

    2. Time to Tumour Progression (TTP) [approximately 36 months]

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

    3. Duration of Response (DR) [approximately 36 months]

      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).

    4. Overall Survival (OR) [approximately 36 months]

      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.

    5. 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]

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

    6. Biomarkers in Serum and Tumor Tissue [approximately 36 months]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Institut Catalá d'Oncologia L'Hospitalet L'Hospitalet de Llobregat Barcelona Spain 08907
    2 Hospital Universitario Marqués de Valdecilla Santander Cantabria Spain 39008
    3 Hospital Provincial de Castellón Castelló Valencia Spain
    4 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    5 Hospital Universitario Virgen de las Nieves Granada Spain 18014
    6 Hospital Universitario Ramón y Cajal Madrid Spain 28034
    7 Hospital Universitario 12 de Octubre Madrid Spain 28041
    8 Hospital Universitario La Paz Madrid Spain 28046
    9 Hospital Universitario Virgen de la Victoria Málaga Spain 29010
    10 Hospital Universitario Virgen del Rocío Sevilla Spain 41013

    Sponsors and Collaborators

    • Grupo Espanol de Tumores Neuroendocrinos
    • Threshold Pharmaceuticals
    • Pfizer

    Investigators

    • Study Chair: Enrique Grande, MD, Grupo Espanol de Tumores Neuroendocrinos

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Grupo Espanol de Tumores Neuroendocrinos
    ClinicalTrials.gov Identifier:
    NCT02402062
    Other Study ID Numbers:
    • GETNE-1408
    • 2014-004072-30
    First Posted:
    Mar 30, 2015
    Last Update Posted:
    Jul 27, 2020
    Last Verified:
    Jul 1, 2020
    Keywords provided by Grupo Espanol de Tumores Neuroendocrinos
    pNET
    Additional relevant MeSH terms:
    Neuroendocrine Tumors
    Pancreatic Neoplasms
    Sunitinib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Meeting eligibility criteria: 17 patients that meet the eligibility criteria were finally included
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Period Title: Overall Study
    STARTED 17
    COMPLETED 17
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Overall Participants 17
    Age (Years) [Median (Standard Deviation) ]
    Median (Standard Deviation) [Years]
    60.78
    (10.78)
    Sex: Female, Male (Count of Participants)
    Female
    6
    35.3%
    Male
    11
    64.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    17
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (Count of Participants)
    Spain
    17
    100%
    ECOG PS (Count of Participants)
    grade 0
    11
    64.7%
    grade 1
    6
    35.3%
    Electrocardiogram (ECG) (Count of Participants)
    Count of Participants [Participants]
    17
    100%
    Left ventricular ejection fraction (LVEF) (Count of Participants)
    Count of Participants [Participants]
    17
    100%
    Abbreviated Charlson comorbidity index (Count of Participants)
    index 2
    11
    64.7%
    index 3
    4
    23.5%
    index 4
    2
    11.8%
    Peripheral arterial disease (Count of Participants)
    Yes
    1
    5.9%
    No
    16
    94.1%
    Diabetes (Count of Participants)
    Yes
    5
    29.4%
    No
    12
    70.6%
    Tumor histological grade (Count of Participants)
    Grade I
    2
    11.8%
    Grade II
    15
    88.2%
    Ki-67 index (Count of Participants)
    >10%
    8
    47.1%
    >2%-5%
    5
    29.4%
    >5%-10%
    4
    23.5%
    Mitosis 10 HPF (Count of Participants)
    Unknown
    6
    35.3%
    <2
    6
    35.3%
    2-20
    5
    29.4%
    Primary tumor surgery (Count of Participants)
    Yes
    6
    35.3%
    No
    11
    64.7%
    Tumor stage at diagnosis (Count of Participants)
    II
    3
    17.6%
    III
    1
    5.9%
    IV
    13
    76.5%
    Tumor relapse location (Count of Participants)
    Hepatic
    12
    70.6%
    Extra-hepatic
    1
    5.9%
    Unknown
    4
    23.5%
    Somatostanine analogues prior the trial (Count of Participants)
    Yes
    7
    41.2%
    No
    10
    58.8%
    Baseline concomitant medication (Count of Participants)
    Yes
    16
    94.1%
    No
    1
    5.9%
    Weight (Kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kg]
    70.97
    (15.01)
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    166.71
    (7.74)
    Body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    25.46
    (4.75)
    Body surface area (BSA) (m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [m^2]
    1.79
    (0.2)
    Blood pressure systolic (BPs) (mm Hg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm Hg]
    134.82
    (10.95)
    Blood pressure diastolic (BPd) (mm Hg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm Hg]
    79.12
    (7.42)
    Haemoglobin (g/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/dL]
    13.82
    (1.21)
    White blood cells (x10^9 cells/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [x10^9 cells/L]
    6.22
    (2.17)
    Absolute neutrophil count (x10^9 cells/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [x10^9 cells/L]
    4.52
    (1.84)
    Absolute Lymphocytes count (x10^9 cells/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [x10^9 cells/L]
    1.69
    (0.41)
    Platelet count (x10^9 cells/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [x10^9 cells/L]
    202.94
    (77.34)
    Sodium blood levels (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    139.22
    (3.06)
    Potassium blood levels (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    4.35
    (0.35)
    Calcium blood levels (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    9.18
    (1.83)
    Magnesium blood levels (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    1.9
    (0.38)
    Glucose (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    133.44
    (59.92)
    Creatinine (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    0.76
    (0.17)
    Aspartate AST (SGOT) (u/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [u/L]
    48.95
    (40.18)
    Alanine transaminase ALT (SGPT) (u/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [u/L]
    69.63
    (61.12)
    AST (SGOT)/ ALT (SGPT) (baseline) (Ratio (arbitrary units)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Ratio (arbitrary units)]
    0.83
    (0.30)
    Total bilirubin (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    0.86
    (0.58)
    Gamma-glutamyltransferase (GGT) (u/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [u/L]
    351.25
    (488.76)
    Alkaline phosphatase (AP) (u/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [u/L]
    201.64
    (183.95)
    Albumin (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    4.28
    (0.43)
    Lactate dehydrogenase (LDH) (u/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [u/L]
    216.88
    (83.41)
    CG a tumor marker (ng/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ng/L]
    474.41
    (626.35)
    Enolase 1 (ng/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ng/mL]
    31.92
    (31.08)
    Time between diagnosis (anatomical pathology) and treatment initiation in months (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    14.12
    (22.72)
    Time between diagnosis (anatomical pathology) and surgery in months (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    1.1
    (2.94)
    Time between diagnosis (anatomical pathology) and CT relapse in months (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    8.9
    (13.77)

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate
    Description 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
    Time Frame approximately 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Measure Participants 17
    CR or PR
    3
    17.6%
    SD or PD
    14
    82.4%
    2. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description 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.
    Time Frame approximately 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Measure Participants 17
    Median (95% Confidence Interval) [months]
    10.38
    3. Secondary Outcome
    Title Time to Tumour Progression (TTP)
    Description It is defined as the time between the start of study treatment to date of the first objective evidence of radiological progression.
    Time Frame approximately 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Measure Participants 17
    Median (Full Range) [months]
    5.32
    4. Secondary Outcome
    Title Duration of Response (DR)
    Description 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).
    Time Frame approximately 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Measure Participants 3
    Median (Full Range) [months]
    18.48
    5. Secondary Outcome
    Title Overall Survival (OR)
    Description 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.
    Time Frame approximately 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Measure Participants 17
    Median (95% Confidence Interval) [months]
    32.32
    6. Secondary Outcome
    Title Safety (Adverse Events)
    Description Safety will be assessed according to the reports of adverse events, the frequency of treatment discontinuations due to adverse events, laboratory evaluations or ECG
    Time Frame time between the date of signing the informed consent until 28 days after the last dose of study drug, , an average of 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Measure Participants 17
    SAE
    3
    Deaths (all causes)
    3
    Deaths (SAE related)
    1
    AE
    17
    treatment discontinuation due to toxicity
    4
    7. Secondary Outcome
    Title Biomarkers in Serum and Tumor Tissue
    Description Assess the predictive/prognostic value of the analysed biomarkers in plasm and tumour.
    Time Frame approximately 36 months

    Outcome Measure Data

    Analysis Population Description
    we obtained samples from 13 patients for Cg A and 10 patients for Enolase 1
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    Measure Participants 13
    Cg A
    197
    Enolase 1
    15.06

    Adverse Events

    Time Frame The security assessment period was between the date of the signed informed consent and up to 28 days after the last dose of study drug, an average of 2 years
    Adverse Event Reporting Description
    Arm/Group Title TH-302 + Sunitinib
    Arm/Group Description TH-302 + Sunitinib. Single arm Study. 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.
    All Cause Mortality
    TH-302 + Sunitinib
    Affected / at Risk (%) # Events
    Total 3/17 (17.6%)
    Serious Adverse Events
    TH-302 + Sunitinib
    Affected / at Risk (%) # Events
    Total 3/17 (17.6%)
    Blood and lymphatic system disorders
    Aspartate aminotransferase increased 1/17 (5.9%) 1
    Alanine aminotransferase increased subjects affected / exposed 1/17 (5.9%) 1
    Endocrine disorders
    Pancreatitis 1/17 (5.9%) 1
    General disorders
    Fever 1/17 (5.9%) 1
    Fatigue 1/17 (5.9%) 1
    Hepatobiliary disorders
    Biliary duct obstruction 1/17 (5.9%) 1
    Other (Not Including Serious) Adverse Events
    TH-302 + Sunitinib
    Affected / at Risk (%) # Events
    Total 17/17 (100%)
    Blood and lymphatic system disorders
    Neutrophil count decreased 9/17 (52.9%) 9
    Platelet count decreased 5/17 (29.4%) 5
    Alanine aminotransferase increased 3/17 (17.6%) 3
    Blood bilirubin increased 2/17 (11.8%) 2
    Anemia 2/17 (11.8%) 2
    White blood cell decreased 1/17 (5.9%) 1
    Hypocalcemia 1/17 (5.9%) 1
    Bilirrubin increased 1/17 (5.9%) 1
    Aspartate aminotransferase increased 1/17 (5.9%) 1
    Endocrine disorders
    Pancreatitis 1/17 (5.9%) 1
    Eye disorders
    Conjunctivitis 2/17 (11.8%) 2
    Gastrointestinal disorders
    Diarrhea 9/17 (52.9%) 9
    Dyspepsia 3/17 (17.6%) 3
    Gastroesophageal reflux disease 2/17 (11.8%) 2
    Dysphagia 2/17 (11.8%) 2
    Rectal hemorrhage 1/17 (5.9%) 1
    Hemorrhoids 1/17 (5.9%) 1
    Gastrointestinal disorders - Other, specify: aerophagia 1/17 (5.9%) 1
    Gastrointestinal disorders - Other, specify: acute gastroenteritis 1/17 (5.9%) 1
    Gastrointestinal disorders - Other, glossitis 1/17 (5.9%) 1
    Gastrointestinal disorders - Other, Gingivitis 1/17 (5.9%) 1
    Esophagitis 1/17 (5.9%) 1
    Anal ulcer 1/17 (5.9%) 1
    Anal pain 1/17 (5.9%) 1
    General disorders
    Fatigue 14/17 (82.4%) 14
    General disorders and administration site conditions - Other, epigastralgia 3/17 (17.6%) 3
    Fever 3/17 (17.6%) 3
    Dizziness 1/17 (5.9%) 1
    Abdominal pain 1/17 (5.9%) 1
    Infections and infestations
    Constipation 2/17 (11.8%) 2
    Pharyngitis 1/17 (5.9%) 1
    Nail infection 1/17 (5.9%) 1
    Metabolism and nutrition disorders
    Anorexia 7/17 (41.2%) 7
    Dysgeusia 6/17 (35.3%) 6
    Nausea 5/17 (29.4%) 5
    Vomiting 4/17 (23.5%) 4
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/17 (5.9%) 1
    Nervous system disorders
    Headache 4/17 (23.5%) 4
    Myalgia 2/17 (11.8%) 2
    Dysesthesia 2/17 (11.8%) 2
    Peripheral motor neuropathy 1/17 (5.9%) 1
    Paresthesia 1/17 (5.9%) 1
    Psychiatric disorders
    Depression 1/17 (5.9%) 1
    Renal and urinary disorders
    Hematuria 1/17 (5.9%) 1
    Reproductive system and breast disorders
    Vaginal inflammation 2/17 (11.8%) 2
    Reproductive system and breast disorders - Other, genital dryness 1/17 (5.9%) 1
    Respiratory, thoracic and mediastinal disorders
    Mucositis oral 10/17 (58.8%) 10
    Epistaxis 2/17 (11.8%) 2
    Respiratory, thoracic and mediastinal disorders - thoracic pain 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysesthesia syndrome 5/17 (29.4%) 5
    Rash acneiform 4/17 (23.5%) 4
    Skin hypopigmentation 2/17 (11.8%) 2
    Skin and subcutaneous tissue disorders - Other, Erythema 2/17 (11.8%) 2
    Skin induration 1/17 (5.9%) 1
    Skin hyperpigmentation 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders - Other, specify: Unspecified Onycopathy 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders - Other, specify: Psoriasis 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders - Other, Inguinal cutaneous toxicity 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders - Other, facial rash 1/17 (5.9%) 1
    Skin and subcutaneous tissue disorders - Other, eczematous facial rash 1/17 (5.9%) 1
    Erythroderma 1/17 (5.9%) 1
    Dry skin 1/17 (5.9%) 1
    Alopecia 1/17 (5.9%) 1
    Vascular disorders
    Hypertension 6/17 (35.3%) 6
    Vascular disorders - Other, brachial vein thrombosis 2/17 (11.8%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The sponsor commits to the timely dissemination of the results through scientific conferences and publications which will be responsible for the scientific coordinator and the translational study coordinator. The study coordinator reserves the option to choose your position in the different publications and reports that could be carried out of the study. The coordinator of the study will have a secure position within the authors. The rest of IPs will be assigned according to order of recruitment

    Results Point of Contact

    Name/Title Federico Nepote
    Organization MFAR Clinical Research
    Phone 0034934344412 ext 102
    Email investigacion@mfar.net
    Responsible Party:
    Grupo Espanol de Tumores Neuroendocrinos
    ClinicalTrials.gov Identifier:
    NCT02402062
    Other Study ID Numbers:
    • GETNE-1408
    • 2014-004072-30
    First Posted:
    Mar 30, 2015
    Last Update Posted:
    Jul 27, 2020
    Last Verified:
    Jul 1, 2020