Pancreatic Cancer
Conditions
Keywords
Locally advanced pancreatic cancer, oxaliplatin, chemoradiation, 5FU
Brief summary
The intention of this trial is to determine the maximum tolerated of the treatment combination and to evaluate its safety and efficacy.
Detailed description
Previous studies have demonstrated that neoadjuvant chemoradiation can lead to improved survival with a portion of patients proceeding to resection. This trial will incorporate a similar trial structure using newer agents in patients who present with locally advanced unresectable pancreatic cancer. Specifically oxaliplatin will be used owing to its greater activity in comparison to cisplatin and favorable therapeutic index in combination with radiation compared to gemcitabine. In summary, the primary outcome measure of the phase I portion of the trial is to determine the maximum tolerated dose of this combination. Following the determination of this dose, the phase II portion of the trial will characterize the toxicity of this regimen as well as evaluate for long-term efficacy.
Interventions
Sponsors
Sanofi
NYU Langone Health
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
* Pathologically documented pancreatic adenocarcinoma deemed unresectable due to local involvement of vessels or organs * Patients with a clear clinical diagnosis of localized pancreatic cancer deemed unresectable, who have undergone at least 2 biopsies which were not diagnostic of adenocarcinoma, may be entered at the discretion of the principal investigator. * No prior chemotherapy or abdominal radiation therapy. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 * Clinically measurable or evaluable disease. * Life expectancy of at least 12 weeks. * Adequate bone marrow reserve, granulocyte count \>= 1500/uL, platelet count \>= 100,000/uL, hemoglobin \>= 9 g/dL. * Adequate renal function with creatinine =\< 1.5 times upper limit of normal (ULN) * Adequate biliary function with bilirubin \< 3.0 g/dL (including patients who have been bypassed or treated with percutaneous drainage), serum glutamic pyruvic transaminase (SGPT) (alanine transaminase) =\< 2.5 * Age \> 18 years * Signed informed consent. * No known allergy to one of the study drugs * For female patient of childbearing potential, neither pregnant nor breastfeeding, and under active contraception * No prior malignancy within last 5 years * No central nervous system metastases * No peripheral neuropathy \> grade2 * No other serious concomitant illness
Exclusion criteria
* Active infection or uncontrolled infection * Presence of metastatic disease. * Inadequate organ function as discussed above. * Pregnancy * Serious concomitant systemic disorder. * Use of any investigational agent within a month of treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resectability After Chemoradiation | 7.5 weeks | This is the number of patients whose tumors are resectable after the combination treatment of 5FU, oxaliplatin, and radiation (RT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | up to 10 years since the start of the study | This is the time at which 50% of patients are alive from the trial entry . |
Countries
United States
Participant flow
Recruitment details
Total 24 patients were enrolled to this Ph I/II study between June 2004 and December 2009 at New York University Medical Center.
Pre-assignment details
The efficacy and toxicity data were based on both Ph I and II.
Participants by arm
| Arm | Count |
|---|---|
| Oxaliplatin+ 5FU+ Radiation (RT) /Surgery /FOLFOX 6 Concurrent chemoradiation before surgery and FOLFOX6 regimen after surgery:
Radiation (RT) 180cGy daily x 5 days/week x 5 weeks, then additional 540 cGy in 3 fractions over a half week to pancreatic portal;
Combined with :
5FU 200 mg/m\^2 daily by continuous intravenous infusion (CIV) x 5 weeks and weekly Oxaliplatin 60 mg/m\^2, IV for 5 weeks (in Phase I, 30, 40, 50, and 60 mg/m\^2 Oxaliplatin were tested).
Observation for 2 weeks to assess dose-limiting toxicity (DLT)/Response. Surgery if deemed resectable.
Then modified FOLFOX 6 for 6 cycles (2 weeks/cycle):
Day 1 hour 0: Oxaliplatin 85 mg/m\^2 intravenously (IV) + Leucovorin 350 mg IV over 2 hours; hour 2: 5FU 400 mg/m\^2 IV bolus followed by 2400 mg/m\^2 IV over 46 hours. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Disease progression | 7 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Oxaliplatin+ 5FU+ Radiation (RT) /Surgery /FOLFOX 6 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 63.7 years |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 11 / 24 |
Outcome results
Primary
Resectability After Chemoradiation
This is the number of patients whose tumors are resectable after the combination treatment of 5FU, oxaliplatin, and radiation (RT).
Time frame: 7.5 weeks
Population: Based on intent-to-treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxaliplatin+ 5FU+ Radiation (RT) /Surgery /FOLFOX 6 | Resectability After Chemoradiation | 2 participants |
Secondary
Median Overall Survival
This is the time at which 50% of patients are alive from the trial entry .
Time frame: up to 10 years since the start of the study
Population: Secondary Measure was not reported. Contacted PI. No new Data available.