Pancreatic Cancer
Conditions
Keywords
Advanced Pancreatic Cancer
Brief summary
The primary purpose of this study is to define the maximum tolerated dose of combination docetaxel, gemcitabine, and capecitabine in patients with pancreatic cancer. Adverse effects will be measured in study participants. In addition, researchers will assess data about preliminary efficacy in patients with this treatment approach.
Detailed description
Rationale: Single agent gemcitabine is considered standard care for patients with advanced pancreatic cancer. However, better treatments offering improved outcomes are needed for people with this disease. The combination of docetaxel and capecitabine has shown significant and broad clinical activity in a variety of tumors. Laboratory research on the combination of capecitabine, docetaxel, and gemcitabine indicates synergistic action against tumor cells. The current study will test this combination in patients. The drug administration schedule in this study is aimed at maximizing the potential of activation of capecitabine by both docetaxel and gemcitabine. Treatment: Study participants will be given docetaxel, gemcitabine, and capecitabine. All study drugs will be administered through intravenous infusions in three week cycles. Docetaxel will be given on days 1 and 8, gemcitabine on days 8 and 15, and capecitabine on days 8 through 21. This schedule will be followed by 1 week of rest without administration of study drugs. Since the primary goal of this study is to identify the maximum tolerated dose of the study drugs in combination, patients who enroll in the beginning of the study will receive lower amounts of the study drugs compared to patients who enroll later in the study. Several tests and exams will be given throughout the study to closely monitor patients.
Interventions
DRUGCapecitabine
Will be give on days 8-21
DRUGDocetaxel
Will be given on days 1 and 8,
DRUGGemcitabine
A fixed dose rate will be give on days 8 and 15.
Sponsors
University of Michigan Rogel Cancer Center
Tony Bekaii-Saab
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
* adenocarcinoma of the pancreas * no prior chemo except adjuvant * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 * peripheral neuropathy \</= Gr. 1
Exclusion criteria
* Pregnant/lactating females * Uncontrolled heart disease, diabetes, psychiatric disorder * Therapeutic doses of Warfarin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Weekly up to 24 weeks | MTD will be the dose at which 1 or fewer patients (≤ 1/6) experiences a DLT during the first or second cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing Dose Limiting Toxicities (DLT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Common Toxicities | Weekly up to 24 weeks | The NCI Common Terminology Criteria for Adverse Events version 3.0 was used for adverse event reporting and toxicity grading. |
| Therapeutic Response | every 8 weeks, up to 24 weeks | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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
Patients were enrolled into the study between December 2005 and February 2008.
Pre-assignment details
Patients had histologically or cytologically confirmed metastatic pancreatic adenocarcinoma and measurable disease per RECIST criteria.
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine, Gemcitabine and Docetaxel Docetaxel i.v. over 30 min on days 1 and 8; Capecitabine p.o. in split doses bid on days 8-21, Gemcitabine i.v. over 75 min on days 8 and 15. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Capecitabine, Gemcitabine and Docetaxel |
|---|---|
| Age, Continuous | 59 years |
| Eastern Cooperative Oncology Group (ECOG) ECOG 0 (Fully Active) | 4 patients |
| Eastern Cooperative Oncology Group (ECOG) ECOG 1 (Restricted physical activity) | 17 patients |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD will be the dose at which 1 or fewer patients (≤ 1/6) experiences a DLT during the first or second cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing Dose Limiting Toxicities (DLT).
Time frame: Weekly up to 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine, Docetaxel, Gemcitabine | Maximum Tolerated Dose (MTD) | docetaxel | 36 mg/m^2 |
| Capecitabine, Docetaxel, Gemcitabine | Maximum Tolerated Dose (MTD) | gemcitabine | 750 mg/m^2 |
| Capecitabine, Docetaxel, Gemcitabine | Maximum Tolerated Dose (MTD) | capecitabine | 625 mg/m^2 |
Secondary
Common Toxicities
The NCI Common Terminology Criteria for Adverse Events version 3.0 was used for adverse event reporting and toxicity grading.
Time frame: Weekly up to 24 weeks
Population: grade 3 and grade 4 toxicities according to National Cancer Institute \[NCI\] Common Toxicity Criteria for Adverse Events \[CTCAE\], Version 3.0
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine, Docetaxel, Gemcitabine | Common Toxicities | leukopenia | 29 percent of patients |
| Capecitabine, Docetaxel, Gemcitabine | Common Toxicities | neutropenia | 29 percent of patients |
| Capecitabine, Docetaxel, Gemcitabine | Common Toxicities | fatigue | 25 percent of patients |
Secondary
Therapeutic Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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: every 8 weeks, up to 24 weeks
Population: 3 patients were non-evaluable for response or progression free survival as they withdrew consent after cycle 1 of therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine, Docetaxel, Gemcitabine | Therapeutic Response | Partial Response | 11 percent of patients |
| Capecitabine, Docetaxel, Gemcitabine | Therapeutic Response | Complete Response | 0 percent of patients |
| Capecitabine, Docetaxel, Gemcitabine | Therapeutic Response | Stable Disease | 72 percent of patients |