Trial registered on ANZCTR


Trial ID
ACTRN12616000958482
Ethics application status
Approved
Date submitted
20/06/2016
Date registered
21/07/2016
Date last updated
18/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised Phase II Study Of nab-paclitaxel In Combination With Carboplatin As
First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas
Scientific title
A phase II study to establish if carboplatin and nab-paclitaxel combination is an effective and tolerable chemotherapy treatment for grade 3 advanced gastrointestinal Neuroendocrine Carcinomas.
Secondary ID [1] 289163 0
AG0215NET
Universal Trial Number (UTN)
Trial acronym
NABNEC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Neuroendocrine Carcinomas 298693 0
Condition category
Condition code
Cancer 298749 298749 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Those randomised to the experimental arm will receive:
Intravenous nab-paclitaxel 100 mg/m2 on Day 1 every week and intravenous carboplatin (area under curve equals 5) as per the Calvert formula on Day 1 every 3 weeks until disease progression or unmanageable toxicity.
Intervention code [1] 294689 0
Treatment: Drugs
Comparator / control treatment
Those randomised to the control arm will receive:
Intravenous etoposide 100mg/m2 on Days 1-3 every 3 weeks and intravenous carboplatin (area under curve equals 5) as per the Calvert formula on Day 1 every 3 weeks until disease progression or unmanageable toxicity.
Control group
Active

Outcomes
Primary outcome [1] 298230 0
To determine objective tumour response rate (RR) (partial or complete response as defined by RECIST criteria version 1.1).
Timepoint [1] 298230 0
The time point for objective tumour response rate (RR is 6 months after the last patient has been enrolled)
Secondary outcome [1] 323613 0
To determine the rate of progression free survival (PFS)
Timepoint [1] 323613 0
Progression free survival (PFS) will be measured from date of patient randomisation to the date of first evidence of disease progression, the occurrence of new disease or death from any cause. In patients who received treatment on study without a progression date or death, the PFS will be censored on the date of last clinical assessment, tumour assessment or enrolment, whichever is the later event. Disease progression is defined according to the RECIST version 1.1 criteria. The time point for PFS is 6 months after the last patient has been enrolled
Secondary outcome [2] 323614 0
To determine overall survival (OS)
Timepoint [2] 323614 0
Overall survival (OS) is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known follow-up alive. The time point for OS is 3 years after the last patient has stopped treatment.
Secondary outcome [3] 323615 0
To determine safety
Timepoint [3] 323615 0
The NCI Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) will be used to classify and grade the intensity of adverse events after each treatment cycle. This outcome may be assessed until 30 days +/- 7 days after the last dose of treatment.
Secondary outcome [4] 323616 0
To assess quality of life (QoL) using the EORTC QLQ C30 and QLQ-GINET21 questionnaires.
Timepoint [4] 323616 0
Quality of life is assessed every 3 weeks until progression.
Secondary outcome [5] 324406 0
To investigate blood biomarkers as prognostic and/or predictive biomarkers for clinical endpoints including but not limited to circulating tumour cells (enumeration and molecular characterisation) (association of blood biomarkers with clinical endpoints). This is an exploratory outcome.
Timepoint [5] 324406 0
At the end of the trial (when the clinical endpoints are available)
Secondary outcome [6] 324407 0
To investigate tissue biomarkers as prognostic and/or predictive biomarkers for clinical endpoints including but not limited to biomarkers of cell proliferation, adhesion and metastasis, NEC tumour cell molecular characterisation (association of tissue biomarkers with clinical endpoints). This is an exploratory outcome.
Timepoint [6] 324407 0
At the end of the trial (when the clinical endpoints are available)
Secondary outcome [7] 324408 0
To investigate the mutational profile and DNA methylation profile and utility in prognosis (association of profiles with clinical outcomes). This is an exploratory outcome - method to be confirmed.
Timepoint [7] 324408 0
At the end of the trial (when the clinical endpoints are available)
Secondary outcome [8] 324409 0
To investigate the utility of FDG-PET imaging as an early predictor of response (association of early imaging characteristics with RR). This is an exploratory outcome.
Timepoint [8] 324409 0
At the end of the trial (when the clinical endpoints are available)
Secondary outcome [9] 324410 0
To investigate the clinical utility of functional imaging by FDG PET and 68Ga-octreotate PET/CT Scan (association of imaging with PFS and OS). This is an exploratory outcome.
Timepoint [9] 324410 0
At the end of the trial (when the clinical endpoints are available)

Eligibility
Key inclusion criteria
-Adults, aged 18 years and older, with advanced and/or metastatic, unresectable neuroendocrine carcinoma
-Histologically proven (WHO/ ENET) Grade 3 NEC with Ki-67 greater than 20%. (The features of small versus large cell NEC carcinoma will need to be documented and participants with Mixed AdenoneuroEndocrine Carcinomas (MANEC) are eligible if they have G3 elements)
-Tumour sufficiently FDG-avid on the initial staging PET Scan (SUVmax minimum 3.5)
-Measurable disease as assessed by CT scan of the chest, abdomen and pelvis within 21 days prior to commencement of study treatment (according to RECIST 1.1)
-ECOG performance status 0-2
-Adequate bone marrow function (platelets greater than 100 x 109/L; ANC greater than 2 x 109/L; haemoglobin greater than 100 x 109/L)
-Adequate liver function (total bilirubin less than or equal to 1.5 x ULN, ALT/AST less than or equal to 2.5 × ULN, alkaline phosphatases less than or equal to 2.5 ULN). For participants with liver metastases use the following ULN: total bilirubin less than or equal to 2 x ULN, ALT/AST less than or equal to 3.5 × ULN, alkaline phosphatases less than or equal to 3.5 ULN.
-Adequate renal function (creatinine less than or equal to 1.5 ULN)
-Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
-Signed, written informed consent (main study)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-NECs confirmed not to be from gastrointestinal primaries
-Grade 1 and Grade 2 NETs (Ki-67 less than or equal to 20%)
-Suspected pulmonary origin of the NET
-Known hypersensitivity to nab-paclitaxel
-External beam radiotherapy to solitary target lesions. Patients who have received local radiotherapy of non-target lesions for local symptom control within the last 4 weeks must have recovered from any adverse effects of radiotherapy prior to randomization.
-Prior intrahepatic 90Y-microspheres such as SIR-Spheres
-Major surgery/surgical therapy for any cause within 1 month
-Surgical therapy of loco-regional metastases within the last 3 months prior to randomization
-Severe cardiovascular, hepatic, neurologic or renal comorbid conditions
-Previous cytotoxic chemotherapy, or targeted therapy, or biotherapy within the last 4 weeks (excluding SSAs)
-Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated
-Sensory/motor neuropathy greater than or equal to G2, as defined by NCI CTCAE 4.0
-Life expectancy of less than 3 months
-History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment
-Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
-Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Actual
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 7867 0
New Zealand
State/province [1] 7867 0

Funding & Sponsors
Funding source category [1] 293553 0
Government body
Name [1] 293553 0
National Health and Medical Research Council
Address [1] 293553 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 293553 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Trials Group (AGITG)
Address
Locked Bag 77
Camperdown
NSW 1450
Country
Australia
Secondary sponsor category [1] 292369 0
None
Name [1] 292369 0
Address [1] 292369 0
Country [1] 292369 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295022 0
The Northern Sydney Local Health District Human Research Ethics Committee (NSLHD HREC)
Ethics committee address [1] 295022 0
The Northern Sydney Local Health District Human Research Ethics Committee (NSLHD HREC)
Research Office
Level 13 Kolling Building
Reserve Road
Royal North Shore Hospital
St Leonards NSW 2065
Ethics committee country [1] 295022 0
Australia
Date submitted for ethics approval [1] 295022 0
01/02/2016
Approval date [1] 295022 0
24/03/2016
Ethics approval number [1] 295022 0

Summary
Brief summary
The primary purpose of this trial is to evaluate the safety and efficacy of carboplatin plus nab-paclitaxel in comparison with carboplatin plus etoposide chemotherapy for the treatment of gastrointestinal neuroendocrine carcinomas (NECs).
Who is it for? You may be eligible to enrol in this trial if you are aged 18 or over, and have been diagnosed with advanced and/or metastatic, unresectable gastrointestinal neuroendocrine carcinoma (NEC).
Study details All participants enrolled in this trial will be randomly allocated (by chance) to receive either carboplatin plus nab-paclitaxel or carboplatin plus etoposide. Participants receiving carboplatin plus nab-paclitaxel will be required to visit the study site once per week, for weekly administration of nab-paclitaxel plus adminstration of carboplatin once every three weeks. Participants receiving carboplatin plus etoposide will be required to visit the study site for three consecutive days every three weeks for administration of etoposide plus adminstration of carboplatin once every three weeks. Treatment will continue for all participants until disease progression or until side effects become unmanageable. All participants will be reviewed for side effects, outcomes of survival and cancer progression. Blood and tissue samples will also be taken, as well as specialised scans, to identify markers of prognosis and response. It is hoped that the findings of this trial will identify which treatment is the most promising, for further investigation to be undertaken to guide best practice.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65706 0
Dr Mustafa Khasraw
Address 65706 0
NHMRC Clinical Trials Centre
The University of Sydney
Locked Bag 77
Camperdown NSW 1450
Country 65706 0
Australia
Phone 65706 0
+61 2 9562 5000
Fax 65706 0
Email 65706 0
nabnec@ctc.usyd.edu.au
Contact person for public queries
Name 65707 0
Dr Mustafa Khasraw
Address 65707 0
NHMRC Clinical Trials Centre
The University of Sydney
Locked Bag 77
Camperdown NSW 1450
Country 65707 0
Australia
Phone 65707 0
+61 2 9562 5000
Fax 65707 0
Email 65707 0
nabnec@ctc.usyd.edu.au
Contact person for scientific queries
Name 65708 0
Dr Mustafa Khasraw
Address 65708 0
NHMRC Clinical Trials Centre
The University of Sydney
Locked Bag 77
Camperdown NSW 1450
Country 65708 0
Australia
Phone 65708 0
+61 2 9562 5000
Fax 65708 0
Email 65708 0
nabnec@ctc.usyd.edu.au