Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Disease Progression

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Irinotecan

Vitamin A

Retinol palmitate

Dexamethasone

Levoleucovorin

Palonosetron

Aprepitant

Lenograstim

Dexamethasone acetate

Folic Acid

Vitamin B Complex

Folfirinox

Antimetabolites

Retinol

Folinic Acid

Folate

Vitamin B9

Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.

Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.

* Oxaliplatin 85 mg/m2 IV infused over two hours, followed by
* Leucovorin 400 mg/m2 IV over two hours
* Irinotecan 135 mg/m2 IV over 90 minutes (concurrent with leucovorin during the last 90 min of the leucovorin infusion)
* 5-FU 300mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46 hours

FOLFIRINOX is a chemotherapy regimen. It is made up of the following four drugs:

FOL - folinic acid (leucovorin), a vitamin B derivative that modulates/potentiates/reduces the side effects of fluorouracil; F - fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis; IRIN - irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating; and OX - oxaliplatin (Eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis.

Jill Lacy, MD

The primary objective of this study was to determine the progression free survival in patients with metastatic pancreatic cancer and in patients with locally advanced unresectable non-metastatic pancreatic cancer treated with a dose-attenuated modification of folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX). Secondary endpoints included: determine objective response rate according to RECIST; determine overall survival; evaluate toxicity; determine rate of resection in locally advanced unresectable stratum; correlate time to progression, objective response, and overall survival with early changes in glucose metabolism using \[18F\]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scanning.

A phase II open label single arm multi-institutional study at Yale's Smilow Cancer Hospital (New Haven, CT, USA), the Smilow Cancer Hospital Care Centers (regional community-based clinics), the VA Connecticut Healthcare System West Haven Campus (West Haven, CT, USA) and Bridgeport Hospital (Bridgeport, CT, USA). The primary objective of this study was to determine the PFS in patients with MPC and LAPC treated with a dose attenuated modification of FOLFIRINOX.

NOTE: Upon results reporting (2016), the registration record was reorganized to display MPC and LAPC groups in individual arms. The most meaningful comparison is between MPC/LAPC and historical controls. That is how results are reported in the published paper, see citations.

Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

Phase II Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

The primary objective of this study is to determine the progression free survival in patients with metastatic pancreatic cancer and in patients with locally advanced unresectable non-metastatic pancreatic cancer treated with a dose-attenuated modification of FOLFIRINOX. Tumour response was determined according to RECIST 1.1 by independent radiology review.

Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1 by independent radiology review) at 8 week intervals in patients with metastatic disease and in patients with locally advanced disease.

Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.

Toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0. Rates of grade 3 and 4 toxicities will be compared to historical controls. MPC and LAPC are combined because they were given the exact same medication. The study aimed to compare this dosage with historical dosage, so this comparison is the most appropriate.

The rate of surgical resection in the cohort of patients with locally advanced disease will be determined.

The time to progression, objective response rate, and overall survival will be correlated with early changes in glucose metabolism using FDG-positron emission tomography (PET) scanning in patients with metastatic disease and locally advanced disease.

Yale University

Reported below are grade 3 and 4 adverse events reported at greater than 5% per treatment arm collected. Serious Adverse Events and All Cause Mortality are reported for the overall population, while the Adverse Events are reported only for those where toxicity was assessed (1 less participant overall, see Outcome Measures).

MPC Modified FOLFIRINOX

LAPC Modified FOLFIRINOX

Total

Age, Customized

Sex: Female, Male

0: Fully active

1: Restricted in physically strenuous activity

ECOG Performance Status

Head

Body

Tumour Resection

Location of the pancreatic tumour in either the head or body of the pancreas. Six subjects had their pancreatic tumour resected (so it is no longer located in the pancreas), but still qualified for the metastatic arm.

Pancreatic tumour location

Normal

Elevated, <59 Upper Limits of Normal

Elevated, >=59 Upper Limits of Normal

CA 19-9 (carbohydrate antigen 19-9 is a tumor marker that is used primarily in the management of pancreatic cancer. Changes in CA 19-9 levels help determine if the tumor is growing, remaining stable or getting smaller.

Level of CA19.9

Biliary stent

75 patients, including 44 with MPC and 31 with LAPC, were enrolled. The demographics and disease characteristics of the 37 evaluable patients in the MPC cohort in this study are presented here. Seven of 44 patients with MPC were excluded from efficacy analysis due to voluntary withdrawal.

Jill Lacy

Two of 31 patients with LAPC were excluded from efficacy analysis because they did not complete four cycles to reach the first efficacy assessment (one due to cholecystitis with abscess and one due to cerebrovascular accident).

Progression Free Survival

Objective Response Rate

Overall Survival

Neutropenia

Thrombocytopenia

Anaemia

Febrile neutropenia

Diarrhea

Fatigue

Alanine aminotransferase (ALT) increased

Thromboembolic event

Peripheral sensory neuropathy

Vomiting

One of the total 75 patients did not receive treatment and was excluded from toxicity analysis. Treatment-related grade 3 and 4 adverse events observed in our study and in the historical control group treated with standard FOLFIRINOX.

Toxicity

Unresectable

Borderline

Only LAPC patients were considered in the analysis. 13 patients in the LAPC group had surgical resection. The definition of locally unresectable and borderline were clarified in the protocol.

Rate of Resection in Patients With Locally Advanced Disease

This outcome was included in the 2012 protocol registration and actually describes a series of analyses that were not fully conducted, and will not be. The outcome measures described in the outcome description are presented as separated outcome measures elsewhere in this results record.

Correlate Time to Progression, Objective Response, and Overall Survival With Early Changes in Glucose Metabolism Using FDG-positron Emission Tomography (PET) Scanning

Overall Study

Spots Global Cancer Trial Database for Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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