Metastatic Pancreatic Cancer
Conditions
Keywords
newly diagnosed, advanced pancreatic cancer, pancreatic cancer, metastatic pancreatic cancer, pancreas
Brief summary
The purpose of this study is to test the safety, activity and best doses of FOLFOX-A which consists of the standard chemotherapy drugs fluorouracil, leucovorin, oxaliplatin and abraxane. Each of these drugs are currently used in pancreatic cancer. The experimental part of the study is combining these drugs together in FOLFOX-A.
Detailed description
More active treatments are desperately needed in pancreatic cancer. The regimen of FOLFIRINOX increases survival as compared to gemcitabine but at a cost of increased toxicity. Irinotecan is responsible for much of the toxicity of FOLFIROX but may not contribute significantly to the regimen's activity. Abraxane is a new agent in pancreatic cancer. This albumin-bound nanoparticle form of paclitaxel increases tumor accumulation of paclitaxel though binding of albumin to SPARC in pancreatic cancer stroma. The investigators therefore propose a pilot study of FOLFOX (fluorouracil, leucovorin and oxaliplatin) combined with abraxane to establish the safety and preliminary activity of FOLFOX-A. Patients with inoperable (metastatic and locally advanced) pancreatic cancer will be eligible since the primary outcome is to establish the safety of FOLFOX-A.
Interventions
DRUGDose level 1
Abraxane 125 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion
DRUGDose level 2/MTD
Abraxane 150 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion
DRUGDose level 3
Abraxane 175 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion
Sponsors
Lifespan
Rhode Island Hospital
Memorial Hospital of Rhode Island
Brown University
Study design
Allocation
NON_RANDOMIZED
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 confirmed pancreatic ductal adenocarcinoma. * Metastatic or locally advanced disease. * No prior treatment for pancreatic cancer * Radiographically measurable disease. * No major surgery within 4 weeks of the start of study treatment. Patients must have recovered from the side effects of any major surgery at the start of study treatment. Laparoscopy and central venous catheter placement are not considered major surgery. * Patients with serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive FOLFOX-A * Preexisting neuropathy \> grade 1. * No prior invasive malignancy within the prior two years. However, patients with an early stage malignancy that is not expected to require treatment in the next 2 years (such as early stage, resected breast cancer or asymptomatic prostate cancer) are eligible. * ECOG performance status 0 or 1. * Age ≥ 18 years of age. * Not pregnant and not nursing. Women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to beginning of treatment. * Required Initial Laboratory Values: * Neutrophils ≥ 1,500/μl * Platelet count ≥ 100,000/μl * Creatinine ≤ 1.5 mg/dL -or- creatinine clearance ≥ 60 mL/min * Total bilirubin ≤ 1.5 x ULN * AST (SGOT) & ALT (SGPT) ≤ 3.0 x ULN
Exclusion criteria
-Patients with known brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Toxicities to Define MTD of FOLFOX-Abraxane (A) for Newly Diagnosed, Advanced Pancreatic Cancer. | For up to 30 days post completing drug, an expected average of 6 months | MTD (Abraxane 150 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion) was defined by protocol documented and predefined DLT's in 3 dose levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (if Patient's Tumor(s)Are Progressing or Being Controlled) Following Treatment With FOLFOX-A for Patients With Newly Diagnosed, Advanced Pancreatic Cancer. | pre-drug until disease progression, whichever comes first, for an expected average of 6 months | Data below summarizes number of patients who experienced partial response. Partial response evaluated in this study using the international criteria proposed in the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1 Response Criteria Partial Response (PR) At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Dose Level 1 Drug: Dose level 1 Abraxane 125 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion
Other Names:
5-FU infusion, leuocovorin, oxaliplatin, Abraxane | 6 |
| Experimental: Dose Level 2/ MTD Drug: Dose level 2/MTD Abraxane 150 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion
Other Names:
5-FU infusion, leuocovorin, oxaliplatin, Abraxane | 26 |
| Experimental: Dose Level 3 Drug: Dose level 3 Abraxane 175 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion
Other Names:
5-FU infusion, leuocovorin, oxaliplatin, Abraxane | 3 |
| Total | 35 |
Baseline characteristics
| Characteristic | Experimental: Dose Level 2/ MTD | Experimental: Dose Level 3 | Experimental: Dose Level 1 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 1 Participants | 3 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 2 Participants | 3 Participants | 20 Participants |
| Age, Continuous | 63.38 years | 63.33 years | 58.83 years | 61.85 years |
| Region of Enrollment United States | 26 participants | 3 participants | 6 participants | 35 participants |
| Sex: Female, Male Female | 10 Participants | 1 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 16 Participants | 2 Participants | 1 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 19 / 35 |
Outcome results
Primary
Assessment of Toxicities to Define MTD of FOLFOX-Abraxane (A) for Newly Diagnosed, Advanced Pancreatic Cancer.
MTD (Abraxane 150 mg/m2 day 1, Oxaliplatin 85 mg/m2 day 1, leuocovorin 400 mg/m2 day 1, F-FU infusion 1200 mg/m2 day x 2 days IV infusion) was defined by protocol documented and predefined DLT's in 3 dose levels.
Time frame: For up to 30 days post completing drug, an expected average of 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Dose Level 1 | Assessment of Toxicities to Define MTD of FOLFOX-Abraxane (A) for Newly Diagnosed, Advanced Pancreatic Cancer. | 1 participants |
| Experimental: Dose Level 2/ MTD | Assessment of Toxicities to Define MTD of FOLFOX-Abraxane (A) for Newly Diagnosed, Advanced Pancreatic Cancer. | 1 participants |
| Experimental: Dose Level 3 | Assessment of Toxicities to Define MTD of FOLFOX-Abraxane (A) for Newly Diagnosed, Advanced Pancreatic Cancer. | 2 participants |
Secondary
Response Rate (if Patient's Tumor(s)Are Progressing or Being Controlled) Following Treatment With FOLFOX-A for Patients With Newly Diagnosed, Advanced Pancreatic Cancer.
Data below summarizes number of patients who experienced partial response. Partial response evaluated in this study using the international criteria proposed in the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1 Response Criteria Partial Response (PR) At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
Time frame: pre-drug until disease progression, whichever comes first, for an expected average of 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Dose Level 1 | Response Rate (if Patient's Tumor(s)Are Progressing or Being Controlled) Following Treatment With FOLFOX-A for Patients With Newly Diagnosed, Advanced Pancreatic Cancer. | 3 participants |
| Experimental: Dose Level 2/ MTD | Response Rate (if Patient's Tumor(s)Are Progressing or Being Controlled) Following Treatment With FOLFOX-A for Patients With Newly Diagnosed, Advanced Pancreatic Cancer. | 17 participants |
| Experimental: Dose Level 3 | Response Rate (if Patient's Tumor(s)Are Progressing or Being Controlled) Following Treatment With FOLFOX-A for Patients With Newly Diagnosed, Advanced Pancreatic Cancer. | 1 participants |