Stage IIIA Gallbladder Cancer AJCC v7, Stage IIIB Gallbladder Cancer AJCC v7, Stage III Intrahepatic Cholangiocarcinoma AJCC v7, Stage IVA Gallbladder Cancer AJCC v7, Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7, Stage IVB Gallbladder Cancer AJCC v7, Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7, Unresectable Extrahepatic Bile Duct Carcinoma, Unresectable Gallbladder Carcinoma
Conditions
Brief summary
This phase II trial studies how well gemcitabine hydrochloride, cisplatin, and nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) work in treating patients with biliary cancers (which includes the gallbladder and bile ducts inside and outside the liver) that have spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as gemcitabine hydrochloride, cisplatin, and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. Determine the progression-free survival (PFS) of gemcitabine hydrochloride (gemcitabine), cisplatin, and nab-paclitaxel in advanced, untreated biliary cancers (intrahepatic cholangiocarcinomas, extrahepatic cholangiocarcinomas, and gallbladder cancers). SECONDARY OBJECTIVES: I. Determine the response rate (RR) and disease control rate (partial response + complete response + stable disease) of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers. II. Determine overall survival (OS) of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers. III. Evaluate the toxicity of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers. EXPLORATORY OBJECTIVES: I. Correlate the carbohydrate antigen (CA) 19-9 response (defined as \>50% decrease from baseline) with tumor response, PFS and OS. II. Assess ribonucleotide reductase subunit MI (RRMI), excision repair cross-complementation group 1 (ERCC1) pre-treatment status and correlate with tumor response, PFS and OS on an exploratory basis. III. Collect optional blood and tissue at the start of treatment and at progression to explore mechanisms of resistance. OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.
Interventions
DRUGCisplatin
Given IV
DRUGGemcitabine Hydrochloride
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGNab-paclitaxel
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have histologically or cytologically confirmed intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer or may undergo a repeat biopsy for histologic confirmation if pre-existing biopsy is not sufficient for diagnosis * Metastatic or unresectable disease documented on diagnostic imaging studies * May not have received prior chemotherapy; if patient has received prior adjuvant therapy, must be \> 6 months from treatment * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 * Platelets \>= 100,000/ul * Hemoglobin \> 9.0 g/dL * Total bilirubin =\< 1.5 mg/dL (in patients with known Gilbert's syndrome direct bilirubin =\< 1.5 x upper limit of normal \[ULN\] will be used as organ function criteria, instead of total bilirubin) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = \< 5 x ULN * Creatinine =\< 1.5 gm/dL * Negative serum or urine pregnancy test in women with childbearing potential (WOCBP) defined as not post-menopausal for 12 months or no previous surgical sterilization, within one week prior to initiation of treatment; WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy * A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy; if the partner is pregnant or breastfeeding, the subject must use a condom * Patients must sign an informed consent and authorization indicating that they are aware of the investigational nature of this study and the known risks involved
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) * Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection * Pregnancy (positive pregnancy test) or lactation * Known central nervous system (CNS) disease, except for treated brain metastasis; treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) during the screening period; anticonvulsants (stable dose) are allowed; treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator \[LINAC\], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) | up to 3 years | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) | up to 3 years | The Kaplan-Meier method was used to estimate OS, with surviving patients censored at the time of surgery or at last known follow-up. |
| Number of Participants With Treatment Response Rate | Up to 2 years | Per Response Evaluation Criteria In Solid Tumors Criteria(RECIST v1.1.14) for target lesions and assessed by MRI: Complete Response (CR),Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Countries
United States
Participant flow
Recruitment details
Phase 2 clinical trial conducted at the University of Texas MD Anderson Cancer Center and the Mayo Clinic in Phoenix.
Pre-assignment details
62 participants enrolled, 60 started treatment and 2 did not receive treatment (1) Progressive disease and (1) Withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| High Dosage Gemcitabine 1000mg/m2, Cisplatin 25mg/m2 & Nab-Paclitaxel 125mg/m2 on days 1 & 8 of a 21 day cycle. | 32 |
| Low Dosage Gemcitabine 800mg/m2, Cisplatin 25mg/m2 & Nab-Paclitaxel 100mg/m2 on days 1 & 8 of a 21 day cycle. | 28 |
| Total | 60 |
Baseline characteristics
| Characteristic | Low Dosage | Total | High Dosage |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 11.1 | 58.3 years STANDARD_DEVIATION 11.1 | 58.1 years STANDARD_DEVIATION 11.1 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 28 participants | 60 participants | 32 participants |
| Sex: Female, Male Female | 11 Participants | 27 Participants | 16 Participants |
| Sex: Female, Male Male | 17 Participants | 33 Participants | 16 Participants |
| Tumor Type Extrahepatic cholangiocarcinoma (EHCC) | 5 Participants | 9 Participants | 4 Participants |
| Tumor Type Gallbladder Cancer (GBC) | 9 Participants | 13 Participants | 4 Participants |
| Tumor Type Intrahepatic cholangiocarcinoma (IHCC) | 14 Participants | 38 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 32 | 0 / 28 |
| other Total, other adverse events | 8 / 32 | 9 / 28 |
| serious Total, serious adverse events | 5 / 32 | 1 / 28 |
Outcome results
Primary
Median Progression Free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: up to 3 years
Population: 3 participants are not included due to 2 Discontinued during cycle 1 (adverse event) and 1 Refused treatment following cycle 1 (patient choice). The analysis for PFS were calculated for the total treated population that received both high and low dosage.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High Dosage | Median Progression Free Survival (PFS) | 11.4 months |
| Low Dosage | Median Progression Free Survival (PFS) | 14.9 months |
p-value: 0.62Log Rank
Secondary
Median Overall Survival (OS)
The Kaplan-Meier method was used to estimate OS, with surviving patients censored at the time of surgery or at last known follow-up.
Time frame: up to 3 years
Population: 3 participants are not included due to they were lost to follow up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High Dosage | Median Overall Survival (OS) | 19.5 months |
| Low Dosage | Median Overall Survival (OS) | 15.7 months |
p-value: 0.39Log Rank
Secondary
Number of Participants With Treatment Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria(RECIST v1.1.14) for target lesions and assessed by MRI: Complete Response (CR),Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dosage | Number of Participants With Treatment Response Rate | Unknown | 4 Participants |
| High Dosage | Number of Participants With Treatment Response Rate | Disease Control Rate(DCR) | 25 Participants |
| High Dosage | Number of Participants With Treatment Response Rate | Complete Response(CR) | 0 Participants |
| High Dosage | Number of Participants With Treatment Response Rate | Partial Response (PR) | 14 Participants |
| High Dosage | Number of Participants With Treatment Response Rate | Stable Disease(SD) | 11 Participants |
| High Dosage | Number of Participants With Treatment Response Rate | Progressive Disease(PD) | 3 Participants |
| Low Dosage | Number of Participants With Treatment Response Rate | Stable Disease(SD) | 9 Participants |
| Low Dosage | Number of Participants With Treatment Response Rate | Unknown | 5 Participants |
| Low Dosage | Number of Participants With Treatment Response Rate | Partial Response (PR) | 9 Participants |
| Low Dosage | Number of Participants With Treatment Response Rate | Disease Control Rate(DCR) | 18 Participants |
| Low Dosage | Number of Participants With Treatment Response Rate | Progressive Disease(PD) | 5 Participants |
| Low Dosage | Number of Participants With Treatment Response Rate | Complete Response(CR) | 0 Participants |