CholangiocarcinomaPhase 1/2NCT03943043
Gemcitabine + Oxaliplatin +Nab-paclitaxel in Subjects With Advanced Biliary Tract Cancer
A Phase 1/2 study testing nab-paclitaxel in people with Cholangiocarcinoma, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma
- What is being tested?
- nab-paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteItaly
- Study dates
- 21 Jul 2017to 1 May 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Istituto Clinico Humanitas
Rozzano, Milan, 20089
Armando Santoro, MD, 02 82244080, armando.santoro@humanitas.it
About this study
Official title: 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.
Read the 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.
- Conditions
- Cholangiocarcinoma
- Being tested
- nab-paclitaxel
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nab-paclitaxelDrug
Also called Gemcitabine, Oxaliplatin
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
- level: gemcitabine 1000 mg/m2 + oxaliplatin 80 mg/m2 + nab-paclitaxel 125 mg/m2
- 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.
| Study group | Role | What they receive |
|---|---|---|
| gemcitabine oxaliplatin nab-paclitaxel | Experimental | combination at different dose of gemcitabine, oxaliplatin and nab-paclitaxel Receives: Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum tolerated dose
Determination of the maximum tolerated dose for phase I
Measured: 4 weeks
Secondary outcomes (2)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
The secondary objectives of the study consist in to better define the safety profile as assessed by CTCAE V4.0
Measured: 16 weeks
Number of responder (in term of CR, PR, SD) to GEMOX plus nab-paclitaxel as assessed by RECIST 1.1
Determination of activity of GEMOX plus nab-paclitaxel as assessed by RECIST 1.1
Measured: Maximum of 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start21 Jul 2017
- Primary completion1 Sep 2020 (estimated)
- Study completion1 May 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Armando Santoro, MD, Principal investigator, Istituto Clinico Humanitas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03943043
- Sponsor's protocol ID
- ONC-2016-001
- Other IDs
- 2016-004118-84, 2016
- Status last verified
- Jul 2020
- First submitted
- 9 Apr 2018
- Last updated
- 29 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pressiani T, Balsano R, Giordano L, Milella M, Bergamo F, Bozzarelli S, Noventa S, Ferrrari D, Scartozzi M, Parra HS, Auriemma A, Solda C, Zaniboni A, Zecchetto C, Rizzato MD, Rimassa L, Santoro A. Multicenter phase I/II trial of gemcitabine, oxaliplatin and nab-paclitaxel as first-line treatment for patients with advanced biliary tract cancer. Eur J Cancer. 2024 Aug;207:114196. doi: 10.1016/j.ejca.2024.114196. Epub 2024 Jun 29.
PubMed 38954899
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Phase I-II Trial of Gemcitabine Plus Oxaliplatin and Nab-paclitaxel in Subjects With Advanced (Unresectable or Metastatic) Biliary Tract Cancer
- ClinicalTrials.gov ID
- NCT03943043
- Acronym / sponsor ID
- ONC-2016-001
- Conditions
- Cholangiocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 21 Jul 2017 (actual)
- Primary completion
- 1 Sep 2020 (estimated)
- Study completion
- 1 May 2021 (estimated)
- First posted
- 9 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| gemcitabine oxaliplatin nab-paclitaxel | Experimental | Drug: nab-paclitaxelcombination at different dose of gemcitabine, oxaliplatin and nab-paclitaxel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nab-paclitaxelAlso: Gemcitabine, OxaliplatinPhase 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. | Drug | gemcitabine oxaliplatin nab-paclitaxel |
Primary outcome
maximum tolerated dose
Time frame: 4 weeks
Determination of the maximum tolerated dose for phase I
2 secondary outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2020.
- Derived from this study: PubMed 38954899Pressiani T, Balsano R, Giordano L, Milella M, Bergamo F, Bozzarelli S, Noventa S, Ferrrari D, Scartozzi M, Parra HS, Auriemma A, Solda C, Zaniboni A, Zecchetto C, Rizzato MD, Rimassa L, Santoro A. Multicenter phase I/II trial of gemcitabine, oxaliplatin and nab-paclitaxel as first-line treatment for patients with advanced biliary tract cancer. Eur J Cancer. 2024 Aug;207:114196. doi: 10.1016/j.ejca.2024.114196. Epub 2024 Jun 29.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Armando Santoro, MD principal investigator
Istituto Clinico Humanitas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing nab-paclitaxel in people with Cholangiocarcinoma, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Armando Santoro, MD (02 82244080, armando.santoro@cancercenter.humanitas.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
maximum tolerated dose (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03943043, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2020.