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Gemcitabine + Oxaliplatin +Nab-paclitaxel in Subjects With Advanced 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cholangiocarcinoma | Drug: nab-paclitaxel | Phase 1 Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 85 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | July 21, 2017 |
| Estimated Primary Completion Date : | September 1, 2020 |
| Estimated Study Completion Date : | May 1, 2021 |
| 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
Phase II: Gemcitabine plus oxaliplatin plus nab-paclitaxel according to RP2D. Other Names:
|
- maximum tolerated dose [ Time Frame: 4 weeks ]Determination of the maximum tolerated dose for phase I
- 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
- 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
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
| Contact: Armando Santoro, MD | 02 82244080 | armando.santoro@cancercenter.humanitas.it | |
| Contact: Tiziana Pressiani, MD | 02 82244773 | tiziana.pressiani@humanitas.it |
| Italy | |
| Istituto Clinico Humanitas | Recruiting |
| Rozzano, Milan, Italy, 20089 | |
| Contact: Armando Santoro, MD 02 82244080 armando.santoro@humanitas.it | |
| Principal Investigator: | Armando Santoro, MD | Istituto Clinico Humanitas |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 9, 2018 | ||||||||
| First Posted Date ICMJE | May 9, 2019 | ||||||||
| Last Update Posted Date | July 29, 2020 | ||||||||
| Actual Study Start Date ICMJE | July 21, 2017 | ||||||||
| Estimated Primary Completion Date | September 1, 2020 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
maximum tolerated dose [ Time Frame: 4 weeks ] Determination of the maximum tolerated dose for phase I
|
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Gemcitabine + Oxaliplatin +Nab-paclitaxel in Subjects With Advanced Biliary Tract Cancer | ||||||||
| Official Title ICMJE | A Multicenter, Phase I-II Trial of Gemcitabine Plus Oxaliplatin and Nab-paclitaxel in Subjects With Advanced (Unresectable or Metastatic) Biliary Tract Cancer | ||||||||
| Brief 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 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. |
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| 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. |
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Phase 1 Phase 2 |
||||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE | Cholangiocarcinoma | ||||||||
| Intervention ICMJE | 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
Phase II: Gemcitabine plus oxaliplatin plus nab-paclitaxel according to RP2D. Other Names:
|
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| Study Arms ICMJE | Experimental: gemcitabine oxaliplatin nab-paclitaxel
combination at different dose of gemcitabine, oxaliplatin and nab-paclitaxel
Intervention: Drug: nab-paclitaxel
|
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| Publications * | Not Provided | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
85 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | May 1, 2021 | ||||||||
| Estimated Primary Completion Date | September 1, 2020 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | Italy | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT03943043 | ||||||||
| Other Study ID Numbers ICMJE | ONC-2016-001 2016-004118-84 ( EudraCT Number ) |
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| Has Data Monitoring Committee | No | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Istituto Clinico Humanitas | ||||||||
| Study Sponsor ICMJE | Istituto Clinico Humanitas | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE |
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| PRS Account | Istituto Clinico Humanitas | ||||||||
| Verification Date | July 2020 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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