Gemcitabine + Oxaliplatin +Nab-paclitaxel in Subjects With Advanced Biliary Tract Cancer

July 28, 2020 updated by: Istituto Clinico Humanitas

A Multicenter, Phase I-II Trial of Gemcitabine Plus Oxaliplatin and Nab-paclitaxel in Subjects With Advanced (Unresectable or Metastatic) Biliary Tract Cancer

The objective of the study is to determine a new combination of drug that improves the outcome in patients with advanced (unresectable or metastatic) BTC. 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).

The primary objective of the phase II is to determine activity of GEMOX plus nab-paclitaxel. The secondary objectives of the study consist in to better define the safety profile and the outcome of the study treated population.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Systemic chemotherapy is increasingly being applied in cases of biliary tract cancers. A benefit for chemotherapy over best supportive care alone was suggested in a trial that randomly assigned 90 patients with advanced pancreatic or biliary cancer (37 with bile duct cancer) to fluorouracil (FU)-based systemic chemotherapy or best supportive care alone (median survival 6 versus 2.5 months, respectively) (1).

The literature regarding treatment results with specific regimens is limited because most series are small, and many reports consist of a mix of bile duct cancers, gallbladder cancer, ampullary cancer, and either pancreatic or hepatocellular cancers. Although they arise in similar locations, these cancers all have a unique natural history and response to chemotherapy. In general, no single drug or combination has consistently increased median survival beyond the expected six to eight months.

Study Type

Interventional

Enrollment (Anticipated)

85

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Milan
      • Rozzano, Milan, Italy, 20089

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written, signed informed consent
  • Male or female aged 18 years or older
  • Histologically or citologically-confirmed advanced (unresectable or metastatic) BTC (gallbladder cancer, cancer of the extrahepatic bile duct, intrahepatic cholangiocarcinoma and ampullary carcinoma)
  • Measurable or evaluable but non-measurable disease according to RECIST v. 1.1
  • Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 6 months before the trial entry is accepted)
  • Adequate bone marrow, liver, and renal function
  • ECOG PS 0-1
  • Life expectancy of at least 12 weeks
  • Negative serum pregnancy test for women of childbearing potential;
  • 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. 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.
  • Male patients mustn't donate sperm during the treatment with nab-paclitexel and for 6 months after completion of study treatment.
  • Agreement not to donate blood during the study.

Exclusion Criteria:

  • 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)
  • Previous systemic treatment for advanced disease
  • Known symptomatic brain metastases or carcinomatous meningitis
  • Severe or uncontrolled systemic disease and/or active or uncontrolled infection
  • Women who are currently pregnant or breast feeding
  • 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
  • Known hypersensitivity to nab-paclitaxel, gemcitabine, oxaliplatin or any of the excipients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: gemcitabine oxaliplatin nab-paclitaxel
combination at different dose of gemcitabine, oxaliplatin and nab-paclitaxel
Drug: nab-paclitaxel

Phase I dosing regimens:

The dose of treatment will be assigned at the time of enrolment in one of these 3 subsequent dose-levels:

- 1° level: gemcitabine 800 mg/m2 + oxaliplatin 80 mg/m2 + nab-paclitaxel 80 mg/m2 0° level: gemcitabine 1000 mg/m2 + oxaliplatin 80 mg/m2 + nab-paclitaxel 100 mg/m2

  1. level: gemcitabine 1000 mg/m2 + oxaliplatin 80 mg/m2 + nab-paclitaxel 125 mg/m2
  2. level: gemcitabine 1000 mg/m2 + oxaliplatin 80 mg/m2 + nab-paclitaxel 150 mg/m2 each administered on day 1, every 14 day

Phase II:

Gemcitabine plus oxaliplatin plus nab-paclitaxel according to RP2D.

Other Names:
  • Gemcitabine
  • Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
maximum tolerated dose
Time Frame: 4 weeks
Determination of the maximum tolerated dose for phase I
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 16 weeks
The secondary objectives of the study consist in to better define the safety profile as assessed by CTCAE V4.0
16 weeks
Number of responder (in term of CR, PR, SD) to GEMOX plus nab-paclitaxel as assessed by RECIST 1.1
Time Frame: Maximum of 24 weeks
Determination of activity of GEMOX plus nab-paclitaxel as assessed by RECIST 1.1
Maximum of 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Clinico Humanitas

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 21, 2017

Primary Completion (ANTICIPATED)

September 1, 2020

Study Completion (ANTICIPATED)

May 1, 2021

Study Registration Dates

First Submitted

April 9, 2018

First Submitted That Met QC Criteria

May 7, 2019

First Posted (ACTUAL)

May 9, 2019

Study Record Updates

Last Update Posted (ACTUAL)

July 29, 2020

Last Update Submitted That Met QC Criteria

July 28, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONC-2016-001
  • 2016-004118-84 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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