A Randomised Phase II Study Of nab-paclitaxel In Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas
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.
Australasian Gastro-Intestinal Trials Group (AGITG)
58 participants
Nov 17, 2016
Interventional
Conditions
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.
Eligibility
Inclusion Criteria10
- 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 (e.g. SUVmax greater than or equal to 3.5). If avidity is borderline or unclear then contact the NHMRC CTC and Study Chair.
- Measurable disease as assessed by CT scan of the chest, abdomen and pelvis within 21 days prior to randomisation (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 g/L)
- Adequate liver function (total bilirubin less than or equal to 1.5 x ULN, ALT/AST less than or equal to 3 × ULN). For participants with liver metastases use the following ULN: total bilirubin less than or equal to 3 x ULN, ALT/AST less than or equal to 5 × ULN. NB; Patients with inadequate liver function and liver metastases who satisfy all other eligibility criteria may start on a reduced dose level (-1 dose level; see table 5.2.1), upon approval by the Study Chair or delegate. Doses can be increased to the standard starting doses if AST/ALT normalise.
- 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)
Exclusion Criteria16
- 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 2 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 2 years after definitive primary treatment, or in the case of stage 1 tumour/s are undergoing curative resection and there is no indication for chemo- or radiotherapy.
- 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
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
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.
Locations(2)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12616000958482