Gastrointestinal Neuroendocrine Carcinomas Clinical Trial
— NABNECOfficial title:
A Feasibility Study Of NAB-Paclitaxel In Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas
| Verified date | November 2017 |
| Source | Barwon Health |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Gastrointestinal Neuroendocrine Tumours (NETs) are gaining increasing recognition as a highly
prevalent disease, responsive to a number of therapies, some of which are proven in modern
randomised controlled trials, but many of which still require high quality clinical trial
evidence to confirm their effectiveness and guide their use in practice. This study is the
first prospective trial to evaluate modern combination chemotherapy. The study will determine
whether Carboplatin and Paclitaxel NAB is a suitable combination for comparison in a
subsequent randomised controlled phase III international trial.
Given the paucity of randomized studies in NETs, there are no clear evidence based
guidelines. Patients are treated according to guidelines established for small cell lung
cancer, incorporating platinum (cisplatin or carboplatin) based doublet treatment with
etoposide. Although these tumors are initially highly chemosensitive, the natural history of
this disease is such that relapses occur early, which ultimately leads to a very poor
prognosis. Almost all clinical trials investigating cytotoxic chemotherapy in NETs are small
single arm studies and guidelines are derived from expert opinion and from extrapolating
results from small cell lung cancer studies. Prospective clinical trials in this group of
patients needs to be conducted to establish an evidence based standard of care and to improve
the prognosis of this highly aggressive group of tumors.
Participants will receive albumin bound paclitaxel (ABRAXANE®) 100 mg/m2 administered as an
intravenous infusion over 30 minutes on Days 1, 8, and 15 of each 21 day cycle. Carboplatin
will be given at an Area Under the Curve (AUC) = 5 mg/min/mL on Day 1 only of each 21 day
cycle administered over 30 mins, beginning immediately after the completion of albumin bound
paclitaxel administration. Participants can continue treatment at the investigator's
discretion until disease progression, development of an unacceptable toxicity, or withdrawal
of consent.
| Status | Active, not recruiting |
| Enrollment | 4 |
| Est. completion date | October 2020 |
| Est. primary completion date | November 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Male or female with unresectable neuroendocrine carcinoma - Age =18 yrs - Histologically proven neuroendocrine carcinoma (NEC) as defined by the WHO Classification of Tumours of the Digestive System, 4th Ed - including tumours mixed with other malignancies (i.e. MANEC or mixed NEC/SCC). The features of small versus large cell NEC carcinoma will need to be documented. - Tumour sufficiently Fluorodeoxyglucose (FDG)-avid (SUVmax minimum 3.5) on the initial staging PET - Patients with advanced and/ or metastatic disease - Measurable disease as assessed by CT scan of the chest, abdomen and pelvis as per RECIST v 1.1, within 21 days prior to commencement of study treatment - ECOG performance status 0-1 - Adequate haematological, renal and hepatic function (neutrophils =2 × 109/L, platelets =100 × 109/L, hemoglobin =100g/L, total bilirubin = 1.5 x upper limit of normal (ULN), aspartate aminotransferase and alanine aminotransferase =2.5 × ULN, alkaline phosphatases =2.5 ULN, creatinine = 1.5 ULN) - Signed, written informed consent Exclusion Criteria: - NECs confirmed not to be from gastrointestinal primaries and NETs of lower grades (Ki67<20) - Suspected pulmonary origin of the NET e.g., FDG-PET avid lung lesions in patients with NEC liver metastases. - 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 starting treatment. - Prior intrahepatic 90Ymicrospheres such as SIR-Spheres - Major surgery/surgical therapy for any cause within 1 month or surgical therapy of loco-regional metastases within the last 3 months prior to starting treatment - Severe cardiovascular, hepatic, neurologic or renal comorbid conditions - Previous cytotoxic chemotherapy, or targeted therapy, or biotherapy for NEC (prior Somatostatin analogs (SSAs) are allowed) - History of hepatitis B or C - Sensory/motor neuropathy = to grade 2, as defined by NCI CTCAE 4.0 - 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Barwon Health | Geelong | Victoria |
| Australia | Royal Melbourne Hospital | Parkville | Victoria |
| Australia | Royal North Shore Hospital | St Leonards | New South Wales |
| Lead Sponsor | Collaborator |
|---|---|
| Barwon Health | Australasian Gastro-Intestinal Trials Group, Deakin University, Specialised Therapeutics Australia |
Australia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Response rate | The objective tumour response rate (partial or complete response as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1) via CT until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | |
| Secondary | Progression free survival | The rate of progression free survival (PFS). (PFS defined from time of registration to disease progression as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1). | From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months | |
| Secondary | Overall survival | Overall survival (OS) (death from any cause). | From date of registration until date of death from any cause, assessed up to 36 months | |
| Secondary | Rates of adverse events as defined by NCI- Common Terminology Criteria for Adverse Events (CTCAE) V4.0 | During study drug administration until 30 days after last study drug dose |