A multicenter, phase I-II trial of gemcitabine plus oxaliplatin and nbb-paclitaxel in subjects with advanced (unresectable or metastatic) biliary tract cancer

Phase 1

• Conditions: Advanced (unresectable or metastatic) biliary tract cancer; MedDRA version: 20.0Level: PTClassification code 10073073Term: Hepatobiliary cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004118-84-IT
• Lead Sponsor: IRCCS ISTITUTO CLINICO HUMANITAS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-09-17
• Last Update Posted: 24 September 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

1.Written, signed informed consent
2.Male or female aged 18 years or older
3.Histologically or citologically-confirmed advanced (unresectable or metastatic) BTC (gallbladder cancer, cancer of the extrahepatic bile duct, intrahepatic cholangiocarcinoma and ampullary carcinoma)
4.Measurable or evaluable but non-measurable disease according to RECIST v. 1.1
5.Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 6 months before the trial entry is accepted)
6.Adequate bone marrow, liver, and renal function
7.ECOG PS 0-1
8.Life expectancy of at least 12 weeks
9.Negative serum pregnancy test for women of childbearing potential;
10.Adoption of adequate contraceptive methods when applicable :
?Women of child-bearing potential must use the following adequate contraceptive methods during all the study and for 1 month after completion of study treatment: abstinence, tubal ligation, oral contraception or transdermal contraceptives, copper intrauterine device, vasectomy of the partner. It is unknown whether the experimental drugs interact or have effect on the hormonal contraceptives functioning: if patients are using hormonal contraceptives, must be associated a barrier method of contraception.
?For male patients with female partners of childbearing potential, agreement to use a barrier method of contraception from the first dose of treatment and for 6 months after completion of study treatment.
11.Male patients mustn’t donate sperm during the treatment with nab-paclitexel and for 6 months after completion of study treatment.
12.Agreement not to donate blood during the study.

Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1.Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as moderate symptoms; limiting instrumental activities of daily living (ADLs)
2.Previous systemic treatment for advanced disease
3.Known symptomatic brain metastases or carcinomatous meningitis
4.Severe or uncontrolled systemic disease and/or active or uncontrolled infection
5.Women who are currently pregnant or breast feeding
6.Previous or current malignancies of other histologies within the last 3 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
7.Known hypersensitivity to nab-paclitaxel, gemcitabine, oxaliplatin or any of the excipients

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the phase I part of the study is to determine the maximum tolerated dose (MTD) of the combination gemcitabine plus oxaliplatin plus nab-paclitaxel, established in the first cycle of therapy, in order to determine the recommended phase II dose (RP2D).<br>The primary objective of the phase II is to determine activity of GEMOX plus nab-paclitaxel.<br>;Secondary Objective: The secondary objectives of the study consist in to better define the safety profile and the outcome of the study treated population. ;Primary end point(s): Phase I : MTD established in the first cycle of therapy <br>Phase II: PFS at 6 months;Timepoint(s) of evaluation of this end point: Phase I: first cycle<br>Phase II: 6 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Safety and Tolerability;<br>PFS;<br>OS;<br>Objective response rate (ORR);<br>Duration of response;Timepoint(s) of evaluation of this end point: at each visit