A Feasibility Study Of NAB-Paclitaxel In Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas

NCT02215447 | Unknown Phase 2 DMC

• 1 other identifier: ALCC 14.01
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Gastrointestinal Neuroendocrine Carcinomas

Keywords

NAB-paclitaxel; Gastrointestinal Neuroendocrine Carcinomas; phase II; carboplatin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Progression free survival

  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

• Overall survival

  From date of registration until date of death from any cause, assessed up to 36 months

• 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

Study Arms (1)

NAB-Paclitaxel with carboplatin

EXPERIMENTAL

NAB paclitaxel (100 mg/m2 IVI) every week (d1,8,15) in three weekly cycle. Carboplatin (AUC=5 IVI) (d1) in three weekly cycle. Study treatment will continue until progressive disease, unacceptable toxicity, or ceased by patient or clinician preference.

Drug: NAB paclitaxel; Drug: Carboplatin

Interventions

NAB paclitaxel DRUG

100 mg/m2 i.v. every week (d1,8,15) in three weekly cycle Number of Cycles: until progression or unacceptable toxicity develops.

Also known as: Abraxane

NAB-Paclitaxel with carboplatin

Carboplatin DRUG

NAB-Paclitaxel with carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Barwon Health: lead
• Specialised Therapeutics Australia: collaborator
• Deakin University: collaborator
• Australasian Gastro-Intestinal Trials Group: collaborator

Study Sites (3)

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Barwon Health

Geelong, Victoria, 3220, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

MeSH Terms

Interventions

Taxes; Albumin-Bound Paclitaxel; Carboplatin

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes

Study Officials

• Mustafa Khasraw, MD

  Barwon Health

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 13, 2014
• Study Start: May 1, 2015
• Primary Completion: November 1, 2018
• Study Completion: October 1, 2020
• Last Updated: November 22, 2017

Record last verified: 2017-11

Locations

AU (3)