Stage IV Pancreatic Cancer
Conditions
Keywords
pancreatic cancer, pancreatic adenocarcinoma, Stage IV pancreatic cancer, pancreas, pancreatic
Brief summary
The primary objective of this study is to determine the efficacy of nab-paclitaxel plus cisplatin plus gemcitabine for patients with metastatic pancreatic ductal adenocarcinoma (PDA).
Detailed description
This is a phase 1b/2 open-label pilot study evaluating the preliminary efficacy and safety of nab-paclitaxel, cisplatin, and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. An individual cycle of therapy will be defined as Days 1 and 8 every 21 days. Multiple cycles may be administered until the patient is withdrawn from therapy. Overall response rates as well as individual categories of response (complete response-CR, partial response-PR, stable disease-SD and progressive disease-PD) will be determined using RECIST 1.1. Time-to-event endpoints, including progression free survival (PFS) and OS (overall survival) will be assessed using the Kaplan-Meier method. Evaluation of stable disease at 9 weeks will also be assessed. Toxicity (adverse events) will be recorded using the NCI CTCAE (v4.0, May 2009).
Interventions
DRUGnab-paclitaxel
25 mg/m2 given intravenously (IV) on days 1 and 8 of a 21 day cycle
DRUGCisplatin
25mg/m2 (or 50mg/m2) given intravenously (IV) on days 1 and 8 of a 21 day cycle
DRUGgemcitabine
1000mg/m2 given intravenously (IV) on days 1 and 8 of a 21 day cycle
Sponsors
Translational Genomics Research Institute
Honor Health - Clinical Trials
Cancer Research and Biostatistics Clinical Trials Consortium
Pancreatic Cancer Research Team
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
* Age \>18 years of age; male or female. * Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. * Capable of providing informed consent and complying with trial procedures. * Karnofsky Performance Status (KPS) of \>/=70%. * Life expectancy \>/=12 weeks. * Measurable tumor lesions according to RECIST 1.1 criteria. * Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating. Both male and female patients of reproductive potential must agree to use a reliable method of birth control during the study.
Exclusion criteria
* Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. * Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment. * Exposure to any investigational agent within 4 weeks prior to initiation of study treatment. * Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit). * History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for \>/= 5 years. * Laboratory values: Screening serum creatinine \> upper limits of normal (ULN); total bilirubin \> ULN: alanine aminotransferase (ALT) and AST \>/= 2.5 ULN or \>/= 5.0 x ULN if liver metastases are present; absolute neutrophil count \< 1,500/mm3, platelet concentration \< 100,00/mm3, hematocrit level \< 27% for females or \< 30% for males, or coagulation tests (prothrombin time \[PT\], partial thromboplastin time \[PTT\], International Normalized Ratio \[INR\]) \> 1.5 x ULN unless on therapeutic doses of warfarin. * current, serious, clinically significant cardiac arrhythmias as determined by the Investigator. * History of HIV infection. * Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. * Major surgery within 4 weeks prior to initiation of study treatment. Any condition that might interfere with the patient's participation in the study or in the evaluation of the study results. * Any condition that is unstable and could jeopardize the patient's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | 1 yr. | The primary objectives of this study is to pursue treatment of 25 individual patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDA) to evaluate: Complete response rate as defined by computed tomography (CT) scan using RECIST 1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits (from at least \> 2x ULN). We expect to accomplish this in \> or = to 5% of patients. When a complete response (CR) is documented, a confirmatory PET scan will be obtained. If 1 or more of 10 patients demonstrate a complete response (CR), study will continue to enroll to a total of 25 patients. If intolerable adverse events or no clinical benefit are noted in the first 6 patients, study will discontinue enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Related Toxicities | Over the course of the subjects' treatment on study, approx 1 year | Frequency of treatment-related toxicities |
| Percentage Change in CA 19-9 | Over the course of the subjects' treatment on study, approx 1 year | Percentage change in CA 19-9 from baseline values |
| Overall Survival | Over the course of the subjects' treatment and participation in study, approx 18 mos | Overall survival is defined as the time from study enrollment until death from any cause. |
| Progression-Free Survival | Over the course of the subjects' treatment and participation in study, approx 18 mos | Progression-free survival is defined as the time from study enrollment until the first documented tumor progression (using RECIST 1.1 criteria) or death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nab-Paclitaxel+Cisplatin+Gemcitabine This is a Phase Ib/II open-label, pilot study evaluating the preliminary efficacy and safety of Nab-Paclitaxel 125mb/m2, Cisplatin 25mg/m2, and Gemcitabine 1000mg/m2, all administered intravenously (IV) on Days 1 and 8 every 21 days until development of toxicity that is unacceptable in the opinion of the patient or the Investigator or upon disease progression.
Nab-Paclitaxel: 25 mg/m2 given intravenously (IV) on days 1 and 8 of a 21 day cycle
Cisplatin: 25mg/m2 (or 50mg/m2) given intravenously (IV) on days 1 and 8 of a 21 day cycle
Gemcitabine: 1000mg/m2 given intravenously (IV) on days 1 and 8 of a 21 day cycle | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Nab-Paclitaxel+Cisplatin+Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 64.4 years STANDARD_DEVIATION 7.94 |
| CA125 Status at Baseline (if CA19-9 Normal at Baseline) Abnormal | 2 Participants |
| CA125 Status at Baseline (if CA19-9 Normal at Baseline) Normal | 2 Participants |
| CA19-9 Status at Baseline Abnormal | 19 Participants |
| CA19-9 Status at Baseline Normal | 6 Participants |
| CEA Status at Baseline (if CA19-9 Normal at Baseline) Abnormal | 2 Participants |
| CEA Status at Baseline (if CA19-9 Normal at Baseline) Normal | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 21 / 25 |
| other Total, other adverse events | 24 / 25 |
| serious Total, serious adverse events | 12 / 25 |
Outcome results
Primary
Complete Response Rate
The primary objectives of this study is to pursue treatment of 25 individual patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDA) to evaluate: Complete response rate as defined by computed tomography (CT) scan using RECIST 1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits (from at least \> 2x ULN). We expect to accomplish this in \> or = to 5% of patients. When a complete response (CR) is documented, a confirmatory PET scan will be obtained. If 1 or more of 10 patients demonstrate a complete response (CR), study will continue to enroll to a total of 25 patients. If intolerable adverse events or no clinical benefit are noted in the first 6 patients, study will discontinue enrollment.
Time frame: 1 yr.
Population: Best Response on study was assessed for patients with at least one evaluation for response while evaluable during the study. One patient achieved CR 32 days after the last dose on therapy and had a best response of PR prior to this assessment. The patient is identified as having a best response of CR in this table.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Complete Response Rate | CR | 2 Participants |
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Complete Response Rate | PR | 15 Participants |
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Complete Response Rate | SD | 4 Participants |
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Complete Response Rate | PD | 3 Participants |
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Complete Response Rate | N/A | 0 Participants |
Secondary
Overall Survival
Overall survival is defined as the time from study enrollment until death from any cause.
Time frame: Over the course of the subjects' treatment and participation in study, approx 18 mos
Population: All patients were evaluated for overall survival.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Overall Survival | 16.4 months |
Secondary
Percentage Change in CA 19-9
Percentage change in CA 19-9 from baseline values
Time frame: Over the course of the subjects' treatment on study, approx 1 year
Population: All patients with a non-zero CA 19-9 measurement at baseline and at least one CA 19-9 measurement on-study were evaluated for percentage change of CA19-9. Of the 25 patients on study, 22 met the criteria for analysis (one had baseline CA 19-9 of zero; two had no post-baseline CA 19-9 measurements).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Percentage Change in CA 19-9 | -47.7 percentage change CA 19-9 from baseline | Standard Deviation 77.13 |
Secondary
Progression-Free Survival
Progression-free survival is defined as the time from study enrollment until the first documented tumor progression (using RECIST 1.1 criteria) or death from any cause.
Time frame: Over the course of the subjects' treatment and participation in study, approx 18 mos
Population: All patients were evaluated for progression-free survival.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Progression-Free Survival | 10.1 months |
Secondary
Treatment-Related Toxicities
Frequency of treatment-related toxicities
Time frame: Over the course of the subjects' treatment on study, approx 1 year
Population: All patients on study were evaluated for maximum grade of treatment-related toxicity.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Treatment-Related Toxicities | Maximum Grade 3 Treatment-Related Adverse Event | 12 Participants |
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Treatment-Related Toxicities | Maximum Grade 4 Treatment-Related Adverse Event | 9 Participants |
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Treatment-Related Toxicities | Maximum Grade 5 Treatment-Related Adverse Event | 1 Participants |
| Nab-Paclitaxel+Cisplatin+Gemcitabine | Treatment-Related Toxicities | No Grade 3-5 Treatment-Related Adverse Event | 3 Participants |