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出境医 / 临床实验 / NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer
NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer
Study Description
Brief Summary:
This is a study to evaluate the clinical activity of the combination of fluorouracil, leucovorin, and nanoliposomal irinotecan as second-line treatment in patients with advanced biliary tract cancers following gemcitabine and platinum chemotherapy.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Biliary Tract Cancer | Drug: Nanoliposomal Irinotecan Drug: Leucovorin Drug: Fluorouracil | Phase 2 |
Detailed Description:
This is a single arm, open label, multicenter phase II study to evaluate the clinical activity of the combination of fluorouracil, leucovorin, and nanoliposomal irinotecan as second-line treatment in patients with advanced biliary tract cancers following gemcitabine and platinum chemotherapy. Patients with advanced biliary tract cancers who have adequate performance status and adequate hepatic and renal function will be eligible. Patients may have received adjuvant chemotherapy and/or radiation therapy prior to enrolling in the trial, but a minimum of 6 months between adjuvant chemotherapy and this current therapy are required. Patients may continue on study as long as they are tolerating treatment and do not have progression of disease by RECIST v1.1 criteria. Response assessments will occur using imaging (CT or MRI) every 8 weeks.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 44 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | NAPOLI-2: Phase II Study of Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Previously Treated Advanced Biliary Tract Cancer |
| Actual Study Start Date : | July 29, 2019 |
| Estimated Primary Completion Date : | July 31, 2021 |
| Estimated Study Completion Date : | July 31, 2022 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Single Arm
Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days. Leucovorin 400 mg/ IV over 30 minutes, every 14 days. Fluorouracil 2,400 mg/m IV over 46 hours.
|
Drug: Nanoliposomal Irinotecan
Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days
Drug: Leucovorin Leucovorin 400 mg/ IV over 30 minutes, every 14 days.
Drug: Fluorouracil Fluorouracil 2,400 mg/m IV over 46 hours.
|
Outcome Measures
Primary Outcome Measures :
- The efficacy of fluorouracil, leucovorin, and nanoliposomal irinotecan in advanced biliary tract cancers following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 4 months ]Defined as positive if there is no evidence of disease progression (PD) at 4 months, as measured by RECIST v1.1 criteria
Secondary Outcome Measures :
- The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 6 months ]Measured in terms of best overall response rate (ORR).
- The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 6 months ]Measured in terms of median progression-free survival (mPFS).
- The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 6 months ]Measured in terms of median overall survival (mOS).
- The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 6 months ]Measured in terms of median time to disease progression (mTTP).
- The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 6 months ]Measured in terms of disease control rate (DCR).
- The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 6 months ]Measured in terms of median duration of disease control (DDC).
- The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 6 months ]Measured in terms of maximum change in tumor marker, CA19-9.
Other Outcome Measures:
- Blood for the analysis of circulating tumor DNA as a surrogate marker of disease burden. [ Time Frame: 6 months ]Correlation of dynamics of circulating tumor DNA change compared with change in CA19-9.
- Archived tumor tissue using next-generation sequencing (NGS) and immunohistochemistry (IHC) in order to elucidate potential mutational biomarkers predictive of response to fluorouracil, leucovorin, and nanoliposomal irinotecan. [ Time Frame: 6 months ]Correlation of tumor genetic mutations and protein expression levels with progression-free survival.
Eligibility Criteria
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Pathologically-confirmed biliary tract cancer (cholangiocarcinoma or gallbladder adenocarcinoma), unresectable or metastatic
- Disease progression on or intolerance of gemcitabine- and platinum-based chemotherapy
- No more than 1 prior line of chemotherapy for unresectable or metastatic disease (adjuvant therapy does not count)
- Measurable disease by RECIST v1.1 criteria
- ECOG performance status of 0-1
- At least 18 years of age
- HIV-positive patients are eligible provided: Stable HAART regimen, No concurrent prophylactic antibiotics or antifungals, and CD4 count above 250 and undetectable viral load
- Adequate bone marrow, hepatic, and renal function
- Consent to access archived tumor tissue if available (available tissue is not required for enrollment)
Exclusion Criteria:
- Ampullary adenocarcinoma
- Woman who are pregnant or breastfeeding
- Anti-cancer treatment within 3 weeks prior to enrollment
- Prior irinotecan or nanoliposomal irinotecan
- Central nervous system metastases unless stable for at least 4 weeks and at least 2 weeks off corticosteroids
- Exposure to a strong CYP3A4 inducer, strong CYP3A4 inhibitor, or strong UGT1A1 inhibitor within 2 weeks of study start
- Known concurrent malignancy or other malignancy within 3 years except for non-melanomatous skin cancers, prostate or cervical cancers following curative therapy, or superficial bladder cancer
- Bowel obstruction
- Allergy or hypersensitivity to fluoropyrimidines, irinotecan, or nanoliposomal irinotecan
- Clinically significant liver disease: Patients with resolved hepatitis B infection are eligible if HBsAg testing is negative; Patients with resolved hepatitis C infection are eligible if viral RNA PCR is negative
- Severe infections within 4 weeks prior to enrollment
- Major surgery within 4 weeks prior to enrollment
Contacts and Locations
Locations
| United States, District of Columbia | |
| Lombardi Comprehensive Cancer Center, Georgetown University | Recruiting |
| Washington, District of Columbia, United States, 20007 | |
| Contact: Yael Meirovich 202-687-9861 ym419@georgetown.edu | |
| Principal Investigator: Benjamin Weinberg, MD | |
Sponsors and Collaborators
Georgetown University
Ipsen
Investigators
| Study Chair: | Benjamin Weinberg, MD | Georgetown University |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | June 27, 2019 | ||||
| First Posted Date ICMJE | July 2, 2019 | ||||
| Last Update Posted Date | November 24, 2020 | ||||
| Actual Study Start Date ICMJE | July 29, 2019 | ||||
| Estimated Primary Completion Date | July 31, 2021 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
The efficacy of fluorouracil, leucovorin, and nanoliposomal irinotecan in advanced biliary tract cancers following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 4 months ] Defined as positive if there is no evidence of disease progression (PD) at 4 months, as measured by RECIST v1.1 criteria
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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 |
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| Original Other Pre-specified Outcome Measures | Same as current | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer | ||||
| Official Title ICMJE | NAPOLI-2: Phase II Study of Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Previously Treated Advanced Biliary Tract Cancer | ||||
| Brief Summary | This is a study to evaluate the clinical activity of the combination of fluorouracil, leucovorin, and nanoliposomal irinotecan as second-line treatment in patients with advanced biliary tract cancers following gemcitabine and platinum chemotherapy. | ||||
| Detailed Description | This is a single arm, open label, multicenter phase II study to evaluate the clinical activity of the combination of fluorouracil, leucovorin, and nanoliposomal irinotecan as second-line treatment in patients with advanced biliary tract cancers following gemcitabine and platinum chemotherapy. Patients with advanced biliary tract cancers who have adequate performance status and adequate hepatic and renal function will be eligible. Patients may have received adjuvant chemotherapy and/or radiation therapy prior to enrolling in the trial, but a minimum of 6 months between adjuvant chemotherapy and this current therapy are required. Patients may continue on study as long as they are tolerating treatment and do not have progression of disease by RECIST v1.1 criteria. Response assessments will occur using imaging (CT or MRI) every 8 weeks. | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | 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 | Advanced Biliary Tract Cancer | ||||
| Intervention ICMJE |
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| Study Arms ICMJE | Experimental: Single Arm
Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days. Leucovorin 400 mg/ IV over 30 minutes, every 14 days. Fluorouracil 2,400 mg/m IV over 46 hours.
Interventions:
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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 |
44 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | July 31, 2022 | ||||
| Estimated Primary Completion Date | July 31, 2021 (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 | |||||
| Listed Location Countries ICMJE | United States | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT04005339 | ||||
| Other Study ID Numbers ICMJE | 2018-0877 | ||||
| Has Data Monitoring Committee | Yes | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Georgetown University | ||||
| Study Sponsor ICMJE | Georgetown University | ||||
| Collaborators ICMJE | Ipsen | ||||
| Investigators ICMJE |
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| PRS Account | Georgetown University | ||||
| Verification Date | November 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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