Clinical Trial Results:
Phase II study to evaluate efficacy of rechallenge with Sunitinib in Patients with Metastatic Pancreatic Neuroendocrine Tumor (pNETs) well differentiated G1/2 advanced or metastatic who previously failed to sunitinib (The RESUNET Trial)

Trial information Top of page
Trial identification
Sponsor protocol code	GETNE-2016-01
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Grupo Español de Tumores Neuroendocrinos - GETNE
Sponsor organisation address	Calle Balmes 243, Escalera A, 5º1a, Barcelona, Spain, 08006
Public contact	Secretaría Técnica GETNE, Grupo Español de Tumores Neuroendocrinos - GETNE, +34 93 434 44 12,
Scientific contact	Secretaría Técnica GETNE, Grupo Español de Tumores Neuroendocrinos - GETNE, +34 93 434 44 12,
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	16 Apr 2020
Is this the analysis of the primary completion data?	Yes
Primary completion date	23 Oct 2019
Global end of trial reached?	Yes
Global end of trial date	23 Oct 2019
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To evaluate sunitinib efficacy in Patients with Metastatic Pancreatic Neuroendocrine Tumor (pNETs) well differentiated G1/2 advanced or metastatic who previously failed to sunitinib
Protection of trial subjects	Not applicable
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	14 Feb 2017
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Spain: 11
Worldwide total number of subjects	11
EEA total number of subjects	11
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	6
From 65 to 84 years	5
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Patients were recruited in the study from 14th february 2017 until 29th may 2019
Pre-assignment
Screening details	Patients with an advanced or metastatic G1/G2 pancreatic neuroendocrine tumour who have failed treatment with sunitinib for advanced disease and who have received at least one other line of systemic treatment with everolimus.
Period 1
Period 1 title	Overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Non-randomised - controlled
Blinding used	Not blinded
Arms
Arm title	Study treatment
Arm description	Patients received sunitinib 37.5 mg daily administered continuously in 28-day cycles. Co-administration with supportive therapies such as somatostatin analogues to control hypersecretory syndrome secondary to the tumour disease itself was permitted during study treatment. Treatment with sunitinib was maintained until confirmation of tumour progression according to RECIST v1.1 criteria.
Arm type	Experimental
Investigational medicinal product name	Sunitinib
Investigational medicinal product code
Other name
Pharmaceutical forms	Capsule, hard
Routes of administration	Oral use
Dosage and administration details	37.5 mg daily in 28-day cycles until disease progression.
Number of subjects in period 1 Study treatment Started 11 Completed 11

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall trial
Reporting group description	-
Reporting group values Overall trial Total Number of subjects 11 11 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 6 6     From 65-84 years 5 5     85 years and over 0 0 Age continuous Units: years     median (full range (min-max)) 55.0 (36.0 to 75.0) - Gender categorical Units: Subjects     Female 7 7     Male 4 4 Race Units: Subjects     Caucasian 11 11 ECOG-PS Units: Subjects     ECOG-PS 0 5 5     ECOG-PS 1 6 6 TNE Grade Units: Subjects     G1 1 1     G2 9 9     G3 1 1 Number of location per patient Units: Subjects     One 4 4     Two 6 6     Three 1 1 TNM: Stage at initial diagnosis Units: Subjects     IIA 1 1     IIB 1 1     IV 9 9 Octreoscan Evaluation Units: Subjects     Not performed 6 6     Performed (Positive result) 5 5 Previous treatments: Targeted therapies Units: Subjects     Yes 11 11     No 0 0 Previous targeted therapies: Sunitinib Units: Subjects     Yes 11 11     No 0 0 Previous targeted therapies: Everolimus Units: Subjects     Yes 10 10     No 1 1 Previous targeted therapies: Others Units: Subjects     Tremelimumab + Durvalumab 2 2     Lenvatinib 1 1     Palbociclib 1 1     Sandostatin 1 1     Somatuline autogel 1 1     No 5 5 Previous treatments: Surgery Units: Subjects     Yes 9 9     No 2 2 Previous treatments: Radiotherapy Units: Subjects     Yes 0 0     No 11 11 Previous treatments: locoregional therapy The patient was treated with selective hepatic chemoembolization. Units: Subjects     Yes 1 1     No 10 10 Previous chemotherapy: Temozolomide + Capecitabine Units: Subjects     Yes 3 3     No 8 8 Previous chemotherapy: Platine + Etoposide Units: Subjects     Yes 3 3     No 8 8 Previous chemotherapy: Estreptozocine + 5-FU Units: Subjects     Yes 2 2     No 9 9 Previous chemotherapy: Lurbinectidine Units: Subjects     Yes 2 2     No 9 9 Tumor location: Liver Units: Subjects     Yes 10 10     No 1 1 Tumor location: Lymph nodes Units: Subjects     Yes 4 4     No 7 7 Tumor location: Pancreas Units: Subjects     Yes 2 2     No 9 9 Tumor location: Lungs Units: Subjects     Yes 2 2     No 9 9 Weight Units: Kg     median (full range (min-max)) 61.5 (45.6 to 83.2) - Height Units: Cm     median (full range (min-max)) 165.0 (145.0 to 179.0) - Time since first diagnosis Time elapsed in months from date of initial diagnosis to date of patient informed consent. Units: Months     median (full range (min-max)) 58.1 (21.6 to 143.7) - Time since advanced or metastatic disease Time elapsed in months from the date of diagnosis of advanced or metastatic disease to the date of the patient's informed consent. Units: Months     median (full range (min-max)) 58.1 (21.6 to 120.0) - Mitotic index: Ki67 Units: Percentage (%)     median (full range (min-max)) 15.0 (5.0 to 37.0) - Tumor size Units: Mm     median (full range (min-max)) 33.5 (22.0 to 110.0) - Treatment duration Time elapsed in weeks from the date on which the patient receives the first dose of treatment to the date of withdrawal of treatment. Units: Weeks     median (full range (min-max)) 22.6 (8.0 to 69.0) - Dose intensity Amount of Study drug that the patient receives. Units: Mg/week     median (full range (min-max)) 246.6 (169.6 to 262.5) - Relative dose intensity Amount of Study drug that the patient receives in relation to the amount of study drug he/she should receive according to the protocol. Units: Percentage (%)     median (full range (min-max)) 94 (65 to 100) -

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Study treatment
Reporting group description	Patients received sunitinib 37.5 mg daily administered continuously in 28-day cycles. Co-administration with supportive therapies such as somatostatin analogues to control hypersecretory syndrome secondary to the tumour disease itself was permitted during study treatment. Treatment with sunitinib was maintained until confirmation of tumour progression according to RECIST v1.1 criteria.

End points Top of page

Primary: 6 months progression free survival Top of page
End point title	6 months progression free survival [1]
End point description
End point type	Primary
End point timeframe	Since start of treatment until radiological evidence of disease progression.
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: One arm non-controlled clinical trial. Only descriptive analyses performed. No comparisons.
End point values Study treatment Number of subjects analysed 11 Units: Percentage (%)     number (confidence interval 95%) 62.3 (33.7 to 90.9)
No statistical analyses for this end point

Primary: 6 months progression free survival Top of page

Secondary: Overall response rate Top of page
End point title	Overall response rate
End point description	1 of 11 patients show partial response (9.1%)
End point type	Secondary
End point timeframe	Since start of treatment until disease progression, unacceptable toxicity or investigator decision.
End point values Study treatment Number of subjects analysed 11 Units: Percentage (%)     number (confidence interval 95%) 9.1 (0.0 to 26.1)
No statistical analyses for this end point

Secondary: Overall response rate Top of page

Secondary: Clinical benefit Top of page
End point title	Clinical benefit
End point description	Clinical benefit: Complete response + partial response + stable disease. 1 patient experienced partial response. 7 patients experienced stable disease. The amount of both is 8 from 11 patients (72,7%).
End point type	Secondary
End point timeframe	Since start of treatment until disease progression, unacepptable toxicity or investigator decision.
End point values Study treatment Number of subjects analysed 11 Units: Percentage (%)     number (confidence interval 95%) 72.7 (46.4 to 99.0)
No statistical analyses for this end point

Secondary: Clinical benefit Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From start of treatment until end of treatment.
Adverse event reporting additional description	The analysis of adverse events was performed for total number of patients who received at least one dose of sunitinib.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	23.0
Reporting groups
Reporting group title	Study treatment
Reporting group description	-
Serious adverse events Study treatment Total subjects affected by serious adverse events      subjects affected / exposed 2 / 11 (18.18%)      number of deaths (all causes) 8      number of deaths resulting from adverse events 0 General disorders and administration site conditions Deterioration of general condition Additional description: Deterioration of general condition Grade 3      subjects affected / exposed 1 / 11 (9.09%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Pyrexia Additional description: Pyrexia Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Study treatment Total subjects affected by non serious adverse events      subjects affected / exposed 11 / 11 (100.00%) Surgical and medical procedures Hypertension Additional description: 1 Hypertension Grade 1 and 1 Grade 2.      subjects affected / exposed 2 / 11 (18.18%)      occurrences all number 2 General disorders and administration site conditions Asthenia Additional description: 4 Asthenia Grade 1 and 3 Grade 2.      subjects affected / exposed 7 / 11 (63.64%)      occurrences all number 7 Face oedema Additional description: Face oedema Grade unknown      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Mucosal inflammation Additional description: Mucosal inflammation Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Xerosis Additional description: Xerosis Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Respiratory, thoracic and mediastinal disorders Dyspnoea Additional description: Dyspnoea Grade 3.      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Investigations Transaminases increased Additional description: Transaminases increased Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Cardiac disorders Congestive cardiac failure Additional description: Congestive cardiac failure grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Nervous system disorders Headache Additional description: Headache Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Dysgeusia Additional description: 1 Dysgeusia Grade 1 and 2 Grade 2.      subjects affected / exposed 3 / 11 (27.27%)      occurrences all number 3 Blood and lymphatic system disorders Leukopenia Additional description: Leukopenia Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Thrombocytopenia Additional description: 1 Thrombocytopenia Grade 1 and 1 Grade 2      subjects affected / exposed 2 / 11 (18.18%)      occurrences all number 2 Neutropenia Additional description: 1 Neutropenia Grade 1 and 2 Grade 3      subjects affected / exposed 3 / 11 (27.27%)      occurrences all number 3 Gastrointestinal disorders Diarrhoea Additional description: 2 Diarrhoea Grade 1, 1 Grade 2 and 1 Grade 3.      subjects affected / exposed 4 / 11 (36.36%)      occurrences all number 4 Abdominal pain Additional description: Abdominal pain Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Abdominal pain upper Additional description: Abdominal pain upper Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Stomatitis Additional description: Stomatitis Grade 3      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Constipation Additional description: Constipation Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Flatulence Additional description: Flatulence Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Nausea Additional description: 2 Nausea Grade 2      subjects affected / exposed 2 / 11 (18.18%)      occurrences all number 2 Vomiting Additional description: Vomiting Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Hepatobiliary disorders Hypertension portal Additional description: Hypertension portal Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Jaundice Additional description: Jaundice Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Skin and subcutaneous tissue disorders Achromotrichia congenital Additional description: Achromotrichia congenital Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Eruption Additional description: Eruption Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Skin hypopigmentation Additional description: Skin hypopigmentation Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Yellow skin Additional description: Yellow skin Grade unknown      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Palmar-plantar erythrodysesthesia syndrome Additional description: 1 Palmar-plantar erythrodysesthesia syndrome Grade 1, 1 Grade 2 and 1 Grade 3      subjects affected / exposed 3 / 11 (27.27%)      occurrences all number 3 Renal and urinary disorders Urinary tract infection Additional description: Urinary tract infection Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Musculoskeletal and connective tissue disorders Arthritis Additional description: 1 Arthritis Grade 1 and 1 Grade 2      subjects affected / exposed 2 / 11 (18.18%)      occurrences all number 2 Back Pain Additional description: Back Pain Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Myalgia Additional description: 1 Myalgia Grade 1 and 1 Grade 2.      subjects affected / exposed 2 / 11 (18.18%)      occurrences all number 2 Infections and infestations Gingivitis Additional description: Gingivitis grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Respiratory tract infection Additional description: Respiratory tract infection grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Tooth infection Additional description: Tooth infection Grade 2      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Metabolism and nutrition disorders Hypercalcemia Additional description: Hypercalcemia Grade 3      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1 Hyperkalaemia Additional description: Hyperkalaemia Grade 1      subjects affected / exposed 1 / 11 (9.09%)      occurrences all number 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
13 Dec 2016	Selection criteria updated
13 Feb 2017	Selection criteria updated
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
Estimated sample size was not reached, which may affect the accuracy of the study results. Not controlled study design.

More information Top of page